Mean Serum FSH Concentrations Research Articles

Stężenia gonadotropin i α podjednostki w surowicy krwi u pacjentów z gruczolakami gonadotropowymi przysadki w zależności od immunoreaktywności guza

Although active gonadotropin-secreting pituitary adenomas are considered very rare, the vast majority of pituitary tumours diagnosed as "non-functioning" express gonadotropins or their free β or α subunits. However, systemic investigations comparing the serum concentrations of follitropin (FSH), lutropin (LH), and α-subunit (αSU) before surgery with the immunoreactivity of the respective substances in the excised tumours are still lacking. Immunostaining of FSH, LH, and αSU was compared in 43 surgically removed gonadotropin - expressing pitu-itary adenomas with serum concentrations of the above-mentioned substances before surgery in the same patients. The serum concentrations of FSH were elevated (> 11.6 mU/mL) in 8/12 (66.7%) cases of FSH-positive adenomas. By contrast, in FSH-negative tumours the elevation of FSH is absent. Moreover, only 1/25 (4%) patients with LH-positive adenoma had the elevated serum concentration of LH (51.5 mU/mL). The overproduction of LH was not observed in adenomas expressing free β LH or in LH-negative tumours. In patients with αSU-positive adenomas elevated serum levels of αSU were observed in 3/15 (20%) cases. No αSU elevations were observed in patients with αSU-negative adenomas. The mean serum FSH, LH, and αSU concentrations were higher in patients with FSH, LH, and/or αSU immunopositive tumours in comparison with immunonegative. However, the differences are not statistically significant. Although "silent" gonadotropinomas constitute a frequent subtype of pituitary adenomas, the "active" subtype (i.e. manifesting by gonadotropin excess) are rare (approx. 4% of all pituitary adenomas). Gonadotropinomas are difficult to diagnose before surgery. The measurement of gonadotropins including αSU is needed but often not sufficient for presurgical diagnosis.

Effects of intracerebroventricular infusions of ghrelin on secretion of follicle-stimulating hormone in peripubertal female sheep.

Reproduction depends on mechanisms responsible for the regulation of energy homeostasis and puberty is a developmental period when reproductive and somatic maturity are achieved. Ghrelin affects the activity of the hypothalamo-pituitary-gonadal axis under conditions of energy insufficiency. An in vivo model based on intracerebroventricular (i.c.v.) infusions was used to determine whether centrally administered acyl ghrelin affects transcriptional and translational activity of FSH in peripubertal lambs and whether ghrelin administration mimics the effects of short-term fasting. Standard-fed lambs received either Ringer-Lock (R-L) solution (120µL h-1) or ghrelin (120µL h-1, 100µg day-1). Animals experiencing a short-term (72h) fast were treated only with R-L solution. In each experimental group, i.c.v. infusions occurred for 3 consecutive days. Immunohistochemistry, in situ hybridisation and real-time reverse transcription quantitative polymerase chain reaction analyses revealed that short-term fasting, as well as exogenous acyl ghrelin administration to standard-fed peripubertal lambs, augmented FSHβ mRNA expression and immunoreactive FSH accumulation. In addition to the effects of ghrelin on FSH synthesis in standard-fed animals, effects on gonadotrophin release were also observed. Acyl ghrelin increased the pulse amplitude for gonadotrophin release, which resulted in an elevation in mean serum FSH concentrations. In conclusion, the present data suggest that ghrelin participates in an endocrine network that modulates gonadotrophic activity in peripubertal female sheep.

Pulsed GnRH secretion and the FSH secretory peaks that initiate ovarian antral follicular wave emergence in anestrous ewes

In ewes, immunization against GnRH blocks LH pulses but mean serum FSH concentrations are only partly reduced; the fate of the FSH peaks that precede ovarian follicular waves has not been studied. In this study, we used immunization against GnRH to examine the need for pulsed GnRH secretion in the genesis of FSH peaks in the anestrous ewe. Six anestrous ewes were given a GnRH immunogen on Day 0 and a booster injection on Day 28. Control ewes ( n = 6) received adjuvant only. Transrectal ultrasonography was performed daily for 2 days prior to and 10 days following both the primary (Days −2 to 10) and booster (Days 26–38) injections and for a 13-day period beginning 26 days after booster injection (Days 54–66). Blood samples were collected daily. Intensive bleeding (every 12 min for 7 h) was performed on Days 9, 37, and 65 of the experimental period to characterize the pulsatile pattern of LH secretion. GnRH antibody titers were increased and LH pulses were abolished immediately after booster immunization ( P < 0.05). The number of FSH peaks, FSH peak concentration and amplitude and basal FSH concentrations were only decreased in immunized ewes in the period of observations starting 26 days after booster immunization ( P < 0.05); however, some peaks were still seen. The number of follicular waves was decreased in the period around booster immunization and no follicular waves were seen during the period starting 26 days after booster immunization in immunized ewes ( P < 0.05). In summary, in anestrous ewes, when pulsed LH secretion was abolished by immunization against GnRH, the peaks in serum concentrations of FSH that trigger ovarian follicular waves continued for a period of time. We concluded that although blocking the effects of GnRH gradually causes a diminution of FSH secretion, there is no acute requirement for GnRH in the regulation of FSH peaks. The existence of FSH peaks in the absence of follicular waves, and pulsed LH secretion, suggests that some endogenous rhythm may drive the occurrence of FSH peaks, independent of both changes in negative feedback by secretory products from ovarian antral follicles and GnRH.

1 PROGESTERONE AS THE DRIVING REGULATORY FORCE BEHIND SERUM FSH CONCENTRATIONS AND ANTRAL FOLLICULAR GROWTH IN CYCLIC EWES

Ovarian antral follicles in sheep grow in an orderly succession, producing typically 3 to 4 follicular waves per 17-day estrous cycle. Each wave is preceded by a transient increase in circulating FSH concentrations. The mechanism controlling the number of recurrent FSH peaks and emerging follicular waves remains unknown. During the ewe's estrous cycle, the time between the first 2 FSH peaks and days of wave emergence is longer than the intervals separating the ensuing FSH peaks and follicular waves. The prolonged inter-peak/inter-wave interval occurs early in the luteal phase when low levels of progesterone are secreted by developing, or non-fully functional, corpora lutea. The purpose of the present study was to determine the effect of varying progesterone (P4) levels on circulating concentrations of FSH and antral follicular development in sheep. Exogenous P4 (15 mg per ewe i.m.) was administered twice daily to 6 cycling Rideau Arcott × Dorset ewes from Day 0 (ovulation) to Day 4 (the mean duration of the inter-wave interval); 6 animals served as controls. Follicular growth was monitored in all animals by daily transrectal ultrasonography (Days 0 to 9). Jugular blood samples were drawn twice a day from Day 0 to 4 and then daily until Day 9 to measure systemic concentrations of P4 and FSH. The first FSH peak post-ovulation was detected on Day 1.4 ± 0.2 and 4.0 ± 0.2 in treated and control ewes, respectively (P &lt; 0.05). The next FSH peak(s) occurred on Days 3.4 ± 0.3 and 5.2 ± 0.2 in the treatment group and on Day 5.5 ± 0.3 in controls. Consequently, the treatment group had, on average, 3 follicular waves emerging on Days 0, 3, and 6, whereas the controls produced 2 waves emerging on Days 0 and 5 (P &lt; 0.05).We then retrospectively analyzed and compared daily serum concentrations of P4 and FSH obtained in cyclic Western White Face ewes (Columbia × Rambouillet) that had 3 (n = 10) or 4 (n = 19) follicular waves per cycle. Mean P4 concentrations were greater (P &lt; 0.05) in sheep with 4 waves per cycle compared with their counterparts, which had 3 waves of follicular growth. Interestingly, the ewes with 3 waves exceeded (P &lt; 0.05) all animals with 4 follicular waves in mean serum FSH concentrations on Days 0 to 2, 6 to 7, and 9 to 15 post-ovulation. In summary, creation of mid-luteal phase levels of P4 in metestrus shortened the time to the first post-ovulatory FSH peak in ewes, resulting in emergence of one more follicular wave compared with control animals during the same time frame. The ewes exhibiting 4 waves of follicular emergence had greater serum levels of P4 but lower FSH concentrations compared with sheep with 3 waves per cycle. Therefore, progesterone appears to be a key endocrine signal governing the control of periodic increases in serum FSH concentrations and the number of follicular waves in cyclic sheep. This study was funded by OMAFRA and NSERC grants. Appreciation is extended to Norman C. Rawlings, Susan Cook, and Sekallu Srinivas (University of Saskatchewan) and the staff at Ponsonby Sheep Research Station.

LH pulse frequency and the emergence and growth of ovarian antral follicular waves in the ewe during the luteal phase of the estrous cycle

BackgroundIn the ewe, ovarian antral follicles emerge or grow from a pool of 2–3 mm follicles in a wave like pattern, reaching greater than or equal to 5 mm in diameter before regression or ovulation. There are 3 or 4 such follicular waves during each estrous cycle. Each wave is preceded by a peak in serum FSH concentrations. The role of pulsatile LH in ovarian antral follicular emergence and growth is unclear; therefore, the purpose of the present study was to further define this role.MethodsEwes (n = 7) were given 200 ng of GnRH (IV) every hour for 96 h from Day 7 of the estrous cycle, to increase LH pulse frequency. Controls (n = 6) received saline. In a second study, ewes (n = 6) received subcutaneous progesterone-releasing implants for 10 days starting on Day 4 of the cycle, to decrease LH pulse frequency. Controls (n = 6) underwent sham surgery. Daily transrectal ovarian ultrasonography and blood sampling was performed on all ewes from the day of estrus to the day of ovulation at the end of the cycle of the study. At appropriate times, additional blood samples were taken every 12 minutes for 6 h and 36 min or 6 h in studies 1 and 2 respectively.ResultsThe largest follicle of the follicular wave growing when GnRH treatment started, grew to a larger diameter than the equivalent wave in control ewes (P < 0.05). Mean serum estradiol and progesterone concentrations were higher but mean serum FSH concentrations were lower during GnRH treatment compared to control ewes (P < 0.05). The increased serum concentrations of estradiol and progesterone, in GnRH treated ewes, suppressed a peak in serum concentrations of FSH, causing a follicular wave to be missed. Treatment with progesterone decreased the frequency of LH pulses but did not have any influence on serum FSH concentrations or follicular waves.ConclusionWe concluded that waves of ovarian follicular growth can occur at LH pulse frequencies lower than those seen in the luteal phase of the estrous cycle but frequencies seen in the follicular phase, when applied during the mid-luteal phase, in the presence of progesterone, do enhance follicular growth to resemble an ovulatory follicle, blocking the emergence of the next wave.

Paraoxonase-1 phenotype in sterile patients with polycystic ovary syndrome. A preliminary report

OBJECTIVE: Polycystic ovary syndrome (PCOS), the most common reproductive endocrinopathy, is associated with an increased risk for the development of diabetes, hypertension and atherosclerosis. Paraoxonase-1 (PON1) is an esterase and lactonase that hydrolyzes lipid peroxides. and has been related with a possible protection from atherosclerosis because of its impact on oxidative stress and inflammatory process. OBJECTIVE: To determine serum PON-1 activity and concentration in sterile women diagnosed of PCOS compared with a group of sterile patients without PCOS. DESIGN: Prospective, randomized study. MATERIALS AND METHODS: From November 2007 to January 2008 13 sterile patients diagnosed of PCOS according withRotterdam criteria and 14 sterile patients without PCOS were included in the study. Anthropometric features, serum concentration of FSH,LH, 17b-estradiol as well as PON 1 activity and concentration were measured at the beginning of the cycle (third tofifth day). All the variables were analyzed using the U de Mann-Whitney test. RESULTS: Mean PON 1activity was 283.2 U/L in the study group and 393.1 U/L in the control group. Mean PON 1 concentration was 101.9 mg/L in the study group and 69.5 mg/L in the control group. Mean BMI was 27.5 in the study group and 22.4 in the control group. Mean of the waist-hip index was 0.81 in the study group and 0.76 in the control group. M mean serum FSH, LH and 17b-estradiol concentrations were 5.75, 9.27 and 48.66 in the study group and 6.97, 4.87 and 40.69 in the control group. There were no cases reported of hypertension. Two patients with diabetes were included in the PCOS group. We found significant differences between the two groups in relation to serum PON 1 activity, weight and BMI (P < 0.01). CONCLUSIONS: Decreased PON1 activity might contribute to an increased risk for cardiovascular disease in women with PCOS in addition to classic risk factors.

EFFECTS OF SUPRA-PHYSIOLOGICAL CONCENTRATIONS OF PROGESTERONE ON THE PATTERNS OF LH SECRETION AND OVARIAN ANTRAL FOLLICULAR WAVE DYNAMICS IN CYCLIC EWES

In the ewe, ovarian antral follicles emerge or grow from a pool of 2–3 mm follicles in a wave like pattern, reaching ≥5mm in diameter before regression or ovulation. There are 3 or 4 such follicular waves during each estrous cycle. Each wave is preceded by a peak in serum FSH concentrations. LH is secreted in a pulsatile manner (1–6 pulses per 6h) but the role of pulsed LH secretion in follicle wave emergence and growth is unclear. Progesterone exerts a negative feedback action on LH secretion. The purpose of the present study was to examine the effect of supra-physiological concentrations of progesterone on LH secretion and antral follicular dynamics. Starting on day 4 of the estrous cycle, six ewes (treatment group) received subcutaneous progesterone-releasing implants for 10 days. Six ewes (control group) underwent sham surgery. Daily transrectal ovarian ultrasonography and blood sampling was performed on all ewes throughout the estrous cycle. Blood samples were also taken every 12 min for 6h on day 3, day 10 and day 16 of the estrous cycle to characterize the LH secretory pattern. Subcutaneous progesteronereleasing implants resulted in supra-physiological concentrations of progesterone in treatment ewes compared to control ewes (5.3 ± 0.4 vs. 2.6 ± 0.2; P<0.05). During the period of implant insertion, the number of LH pulses (0.50 ± 0.2 vs. 1.50 ± 0.2) was lower in treatment ewes compared to control ewes (P<0.05). There was no difference in the number of FSH peaks or the amplitude of the peaks between the treatment and control ewes (P>0.05). Mean serum estradiol and FSH concentrations did not differ between groups (P>0.05). All ewes had normal follicular wave emergence prior to and during implant insertion. There was no difference in the number of follicles 1-2mm, 2mm, 3mm, 4mm, and ≥5mm in diameter between treatment and control ewes (P>0.05). The estrous cycle length tended to be longer in treatment ewes compared to control ewes (19.3 ± 0.6 vs. 18.0 ± 0.4; P=0.1). There was no difference in the ovulation rate between the treatment and control ewes (P>0.05). We concluded that the subcutaneous progesterone releasing implants suppressed pulsatile LH secretion and tended to prolong the estrous cycle length, but did not affect FSH and ovarian antral follicular wave characteristics. Suppressing LH pulse frequency would not appear to affect ovarian antral follicular wave dynamics in cyclic ewes. (platform)

Ultrasonographic study of antral follicle development during sexual maturation in ewe lambs

Eight February-born Suffolk ewe lambs underwent transrectal ovarian ultrasonography every 2 weeks (from 6 to 38 weeks of age) and during seven 10-day periods, with starting dates every 5 weeks (from 6 to 36 weeks of age), to study antral follicle development. Blood samples were taken at 2 and 4 weeks of age, and before each ultrasonographic examination, for radioimmunoassay (RIA) of serum FSH and estradiol, and daily, from 30 weeks of age, for measurement of progesterone. Six ewe lambs reached puberty (defined as an elevation in serum progesterone concentrations ≥0.1 ng/ml for ≥7 days) between 32 and 36 weeks of age (mean ± S.E.M.: 34.0 ± 0.5 weeks). The total number of all follicles ≥2 mm in diameter/ewe lamb increased from 12 to 14 weeks, declined from 24 to 28 weeks, rose from 28 to 32 weeks, and then decreased after 32 weeks of age ( n = 6; P < 0.05). The diameter of the largest follicle increased from 8 to 14 weeks, declined from 14 to 22 weeks, and finally increased between 32 and 36 weeks after birth ( P < 0.05). Mean serum FSH concentrations peaked at 30 weeks and increased again from 14 to 4 weeks before attainment of puberty ( P < 0.05). There were 2.4 ± 0.09 peaks in the daily serum FSH concentrations and 0.8 ± 0.1 emerging follicular waves per lamb (follicles attaining ovulatory diameters of ≥5 mm; P < 0.05) over each 10-day scanning period. The frequency of FSH peaks and follicle wave emergence did not change significantly throughout the study. Mean circulating concentrations of estradiol increased gradually ( P < 0.05) from approximately 6 weeks of age until puberty. It was concluded that antral follicle recruitment and growth increased after the first 8 weeks of age and just before puberty in February-born ewe lambs. A rhythmic pattern of increases in daily serum FSH concentrations, as seen in adult ewes, was present in the ewe lambs of all ages but the pattern of follicular wave emergence was not fully established in pre- and peripubertal ewe lambs.

The relationship between secretory patterns of gonadotrophic hormones and the attainment of puberty in bull and heifer calves born early or late during the spring calving season

It was suggested that an early increase in gonadotrophin secretion in calves aged between 6 and 24 weeks might be critical for initiating developmental changes culminating in puberty. An early rise in luteinizing hormone (LH) release appears to be caused by an increase in LH pulse frequency in bull calves and by an increase in LH pulse amplitude in heifer calves. Previously we have found differences in the characteristics of the LH rise between prepubertal beef calves born in spring or fall; however, age at puberty was not affected by season of birth. Here we report the LH/FSH secretory patterns in prepubertal bull and heifer calves (Hereford x Charolais), born in March or April, respectively (i.e., early or late during the spring calving season; six animals of each sex born at each time). The bull calves of both groups reached puberty (defined as an attainment of scrotal circumference of ≥ 28 cm) at 43.2 ± 1.3 weeks of age ( P > 0.05). Age at puberty for March- and April-born heifer calves (defined as the age at which serum progesterone concentrations first exceeded 0.4 ng/ml) averaged 56.0 ± 1.4 weeks ( P > 0.05). Based on blood samples taken weekly from birth to 26 weeks of age, and then every other week until puberty, bull calves born in March exceeded April-born bull calves in mean serum LH concentrations at 6, 10 and 12 weeks of age ( P < 0.05). Mean FSH concentrations were greater ( P < 0.05) in March-born compared to April-born bull calves from 34 to 32 weeks before puberty. Mean serum LH (at 40, 42 and 56 weeks) and FSH concentrations (at 2, 10, 20, 22–26, 30 and 56 weeks of age) were greater ( P < 0.05) in heifer calves born in April than March. On the basis of frequent blood sampling (every 12 min for 10 h), heifer calves born in April exceeded March-born animals in mean LH and FSH concentrations, at 5 and 25 weeks, and LH pulse frequency, at 5, 10 and 25 weeks of age ( P < 0.05). None of the parameters of LH secretion (i.e., mean concentrations of LH, LH pulse frequency and amplitude based on frequent blood collection) differed between March- and April-born bull calves in this study ( P > 0.05). In summary, March-born bull calves had greater mean serum LH and FSH concentrations prior to 24 weeks of age than April-born calves. April-born heifer calves had greater mean serum concentrations of LH and FSH but this difference was not confined to the early postnatal period. Although there were significant differences in absolute amounts of LH secreted, there were no differences in the frequency of LH secretory pulses amongst March- and April-born bull calves and no differences in LH pulse amplitude in heifer calves born in March or April. As these particular parameters of LH secretion, as well as age at puberty, are not affected by the time or season of birth, they may be primary hormonal cues governing sexual development in bulls and heifers, respectively.

Effects of treatment with LH or FSH from 4 to 8 weeks of age on the attainment of puberty in bull calves

A transient increase in gonadotropin secretion between 6 and 20 weeks of age is critical for the onset of puberty in bull calves. To try and hasten the onset of puberty, bull calves were treated (s.c.) with 3 mg of bLH ( n=6) or 4 mg of bFSH ( n=6) once every 2 days, from 4 to 8 weeks after birth; control calves received saline ( n=6). At 4 and 8 weeks of age, mean LH concentrations were higher ( P<0.05) in bLH-treated (2.3±0.04 ng/ml and 1.20±0.04 ng/ml) as compared to control calves (0.50±0.1 ng/ml and 0.70±0.10 ng/ml). Mean serum FSH concentrations at 4 and 8 weeks of age, were higher ( P<0.05) in bFSH-treated (1.60±0.20 ng/ml and 1.10±0.2 ng/ml) as compared to control calves (0.38±0.07 ng/ml and 0.35±0.07 ng/ml). The age at which scrotal circumference (SC) first reached ≥28 cm, occurred earlier ( P<0.05) in bFSH-treated calves as compared to saline-treated calves (39.3±1.3 and 44.8±1.3 weeks of age, respectively). Based on testicular histology at 56 weeks of age, treatment with bFSH resulted in greater ( P<0.05) numbers of Sertoli cells (5±0.2, 6±0.3 and 5±0.3 in bLH-, bFSH- and saline-treated calves, respectively); elongated spermatids (42±2, 57±8 and 38±5 in bLH-, bFSH- and saline-treated calves, respectively) and spermatocytes (31±3, 38±3 and 29±2 in bLH-, bFSH- and saline-treated calves, respectively) per seminiferous tubule. We concluded that treatment of bull calves with bFSH from 4 to 8 weeks of age increased testicular growth (SC); hastened onset of puberty (SC≥28 cm); and enhanced spermatogenesis.

Comparative endocrinology of cycling and non-cycling Asian ( Elephas maximus) and African ( Loxodonta africana) elephants

Up to 14% of Asian and 29% of African elephants in captivity are not cycling normally or exhibit irregular cycles based on progestin profiles. To determine if ovarian acyclicity is related to other disruptions in endocrine activity, serum pituitary, thyroid, adrenal, and ovarian hormones in weekly samples collected for 6–25 months were compared between normal cycling ( n=22 each species) and non-cycling ( n=6 Asian; n=30 African) elephants. A subset of cycling females ( n=4 Asian, 7 African) also were blood sampled daily during the follicular phase to characterize the peri-ovulatory period. In normal cycling females, two leutinizing hormone (LH) surges were observed 3 weeks apart during a normal follicular phase, with the second inducing ovulation (ovLH). Serum FSH concentrations were highest at the beginning of the non-luteal phase, declining to nadir concentrations within 4 days of the ovLH surge. FSH remained low until after the ovLH surge and then increased during the luteal phase. A species difference was noted in prolactin secretion. In the African elephant, prolactin was increased during the follicular phase, but in Asian elephants concentrations remained stable throughout the cycle. Patterns of thyroid hormones (thyroid-stimulating hormone, TSH; free and total thyroxine, T4; free and total triiodothyronine, T3) and cortisol secretion were not affected by estrous cycle stage or season in cycling elephants. In non-cycling elephants, there were no fluctuating patterns of LH, FSH, or prolactin secretion. Overall mean concentrations of all hormones were similar to those in cycling animals, with the exception of FSH, prolactin, and estradiol. Mean serum FSH concentrations were lower due to females not exhibiting normal cyclic increases, whereas serum estradiol was higher overall in most acyclic females. Prolactin concentrations were significantly increased in 11 of 30 non-cycling females, all of which were African elephants. In sum, while there were no consistent endocrine anomalies associated with ovarian acyclicity, hyperprolactinemia may be one cause of ovarian dysfunction. The finding of elevated estrogens in some acyclic females also deserves further investigation, especially determining how it relates to reproductive tract pathologies.

Effects of 4- tert-octylphenol given in drinking water for 4 months on the male reproductive system of Fischer 344 rats

The environmental pollutant 4- tert-octylphenol (OP) is both toxic and estrogenic to mammalian cells, and injection of OP into adult male rats has devastating effects on their reproductive system. We now report the effects of OP in drinking water (1×10 −5, 1×10 −7 or 1×10 −9 M) on the male reproductive system. Exposure of adult male rats for 4 months to any tested dose of OP had no significant effect on water or food consumption; body weight gain; hematocrit; reproductive organ weights; mean serum LH, FSH or testosterone concentrations; germ cell yield or relative numbers of different classes of testicular cells; or testicular sperm number. In contrast, all doses of OP caused an increase in epididymal sperm with tail abnormalities that would interfere with sperm motility, and the highest dose decreased epididymal sperm number. Our findings raise the possibility that consumption of OP in drinking water may adversely influence male reproductive fertility.

Elevated early follicular gonadotropin levels in women with unexplained infertility do not provide evidence for disordered gonadotropin-releasing hormone secretion as assessed by luteinizing hormone pulse characteristics

Objective To determine whether women with rigorously defined unexplained infertility demonstrated altered GnRH secretion, as reflected by serum LH secretion patterns. Design Prospective observational study. Setting National Center for Infertility Research at Michigan. Patient(s) Nine women with rigorously defined unexplained infertility and 11 healthy, parous age-matched control women. Intervention(s) Gonadotropin-releasing hormone (25 ng/kg) as a bolus injection. Main outcome measure(s) Daytime pulse patterns of LH secretion measured every 10 minutes; mean serum concentrations of LH, FSH, E 2, P, PRL, and cortisol; and response to a physiologic dose of GnRH in the early follicular, late follicular, mid-luteal, and late luteal phases of the same menstrual cycle. Result(s) Serum LH pulse frequency and pulse amplitude and LH secretion in response to a physiologic bolus of GnRH were not significantly different in unexplained infertility patients at any phase of the cycle. Luteinizing hormone pulse frequency and amplitude, as well as response to GnRH, varied significantly across the cycle. Mean early follicular serum LH and FSH concentrations were significantly higher in unexplained infertility patients than in fertile control subjects (LH: 5.31 ± .51 vs. 4.03 ± .33 [mIU/mL ± SEM]; FSH: 5.81 ± .63 vs. 3.80 ± .45) but were not different at any other phase of the cycle. Conclusion(s) These data do not support the hypothesis that unexplained infertility is caused by an abnormality in pulsatile GnRH secretion or abnormal pituitary sensitivity to GnRH. However, the results are consistent with a difference in negative feedback from the ovary to the pituitary in unexplained infertility patients that is suggestive of diminished ovarian reserve.

Gonadotrophin secretion in prepubertal bull calves born in spring and autumn

The reproductive development of bull calves born in spring and autumn was compared. Mean serum LH concentrations in calves born in spring increased from week 4 to week 18 after birth and decreased by week 24. In bull calves born in autumn, mean LH concentrations increased from week 4 to week 8 after birth and remained steady until week 44. LH pulse amplitude was lower in bull calves born in autumn than in calves born in spring until week 24 of age (P < 0.05). There was a negative correlation between LH pulse frequency at week 12 after birth and age at puberty in bull calves, irrespective of season of birth, and LH pulse frequency at week 18 also tended to correlate negatively with age at puberty. Mean serum FSH concentrations, age at puberty, bodyweight, scrotal circumference, testes, prostate and vesicular gland dimensions, and ultrasonographic grey scale (pixel units) were not significantly different between bull calves born in autumn and spring. However, age and body-weight at puberty were more variable for bull calves born in autumn (P < 0.05). In a second study, bull calves born in spring received either a melatonin or sham implant immediately after birth and at weeks 6 and 11 after birth. Implants were removed at week 20. Mean LH concentrations, LH pulse frequency and amplitude, mean FSH concentrations and age at puberty did not differ between the two groups. No significant differences between groups in the growth and pixel units of the reproductive tract were observed by ultrasonography. In conclusion, although there were differences in the pattern of LH secretion in the prepubertal period between bull calves born in autumn and spring, the postnatal changes in gonadotrophin secretion were not disrupted by melatonin treatment in bull calves born in spring. Reproductive tract development did not differ between calves born in spring and autumn but age at puberty was more variable in bull calves born in autumn. LH pulse frequency during the early prepubertal period may be a vital factor in determining the age of bull calves at puberty.

Gonadotrophin secretion in prepubertal bull calves born in spring and autumn

The reproductive development of bull calves born in spring and autumn was compared. Mean serum LH concentrations in calves born in spring increased from week 4 to week 18 after birth and decreased by week 24. In bull calves born in autumn, mean LH concentrations increased from week 4 to week 8 after birth and remained steady until week 44. LH pulse amplitude was lower in bull calves born in autumn than in calves born in spring until week 24 of age (P &lt; 0.05). There was a negative correlation between LH pulse frequency at week 12 after birth and age at puberty in bull calves, irrespective of season of birth, and LH pulse frequency at week 18 also tended to correlate negatively with age at puberty. Mean serum FSH concentrations, age at puberty, bodyweight, scrotal circumference, testes, prostate and vesicular gland dimensions, and ultrasonographic grey scale (pixel units) were not significantly different between bull calves born in autumn and spring. However, age and body-weight at puberty were more variable for bull calves born in autumn (P &lt; 0.05). In a second study, bull calves born in spring received either a melatonin or sham implant immediately after birth and at weeks 6 and 11 after birth. Implants were removed at week 20. Mean LH concentrations, LH pulse frequency and amplitude, mean FSH concentrations and age at puberty did not differ between the two groups. No significant differences between groups in the growth and pixel units of the reproductive tract were observed by ultrasonography. In conclusion, although there were differences in the pattern of LH secretion in the prepubertal period between bull calves born in autumn and spring, the postnatal changes in gonadotrophin secretion were not disrupted by melatonin treatment in bull calves born in spring. Reproductive tract development did not differ between calves born in spring and autumn but age at puberty was more variable in bull calves born in autumn. LH pulse frequency during the early prepubertal period may be a vital factor in determining the age of bull calves at puberty.

An ultrasound-aided study of temporal relationships between the patterns of LH/FSH secretion, development of ovulatory-sized antral follicles and formation of corpora lutea in ewes

To characterize the pulsatile secretion of LH and FSH and their relationships with various stages of follicular wave development (follicles growing from 3 to ≥5 mm) and formation of corpora lutea (CL), 6 Western white-faced ewes underwent ovarian ultrasonography and intensive blood sampling (every 12 min for 6 h) each day, for 10 and 8 consecutive days, commencing 1 and 2 d after estrus, respectively. Basal serum concentrations of LH and LH pulse frequency declined, whereas LH pulse duration and FSH pulse frequency increased by Day 7 after ovulation (P<0.05). LH pulse amplitude increased (P<0.05) at the end of the growth phase of the largest ovarian follicles in the first follicular wave of the cycle. The amplitude and duration of LH pulses rose (P<0.05) 1 d after CL detection. Mean and basal serum FSH concentrations increased (P<0.05) on the day of emergence of the second follicular wave, and also at the beginning of the static phase of the largest ovarian follicles in the first follicular wave of the cycle. FSH pulse frequency increased (P<0.05) during the growth phase of emergent follicles in the second follicle wave. The detection of CL was associated with a transient decrease in mean and basal serum concentrations of FSH (P<0.05), and it was followed by a transient decline in FSH pulse frequency (P<0.05). These results indicate that LH secretion during the luteal phase of the sheep estrous cycle reflects primarily the stage of development of the CL, and only a rise in LH pulse amplitude may be linked to the end of the growth phase of the largest follicles of waves. Increases in mean and basal serum concentrations of FSH are tightly coupled with the days of follicular wave emergence, and they also coincide with the end of the growth phase of the largest follicles in a previous wave, but FSH pulse frequency increases during the follicle growth phase, especially at mid-cycle.

Fasting suppresses pulsatile luteinizing hormone (LH) secretion and enhances orderliness of LH release in young but not older men.

Pulsatile gonadotropin secretion and sex-steroid concentrations are suppressed reversibly in young fasted or malnourished human subjects. In this study, we investigated the impact of age on the dynamic neuroendocrine mechanisms underlying this stress response in healthy young (age, 28 +/- 3 yr, n = 8) vs. older (age 67 +/- 2 yr, n = 8) men with similar body mass indices (mean, 26 +/- 0.6 vs. 26 +/- 1.3 kg/m2, respectively). Serum LH concentrations were measured by immunoradiometric assay (IRMA) in blood collected at 10-min intervals over 27 h on a control (fed) day and on the third day of a 3.5-day fast (water only) assigned in randomized order. After 24 h of basal sampling, GnRH (10 micrograms i.v. bolus) was administered to test gonadotrope responsiveness. Cortisol, dehydroepiandrosterone sulfate, androstenedione, testosterone, FSH, GH, and PRL were measured in 24-h pooled serum as positive and negative control hormones. Approximate entropy was used to quantitate the orderliness of LH release over 24 h, and a multiple-parameter deconvolution method was applied to quantify pulsatile LH secretion and LH half-life. In the fed state, older men exhibited elevated mean (24-h pooled) serum FSH and cortisol concentrations compared with young controls but equivalent serum LH concentrations and reduced serum GH, free testosterone, androstenedione, and dehydroepiandrosterone sulfate concentrations. Fed older men also manifested a lower frequency and amplitude of 24-h pulsatile LH secretion, and, by approximate entropy calculations, a more disorderly pattern of basal LH release than younger individuals. Three- and one-half days of fasting evoked 40% and 47% increases in mean (24-h) serum cortisol concentrations in young and older men, respectively (P < 0.01 vs. fed, but P = not significant for percentage rise in older vs. young men). Concurrently, fasting induced a 2.1-fold fall in the 24-h endogenous LH production rate in young men (fed 36 +/- 9.7 vs. fasted 17 +/- 2.0 IU/L of distribution volume/day, P < 0.01), but did not significantly affect the daily LH secretion rate in older men (fed 27 +/- 4.5 vs. fasted 21 +/- 3.4 IU/day). The reduced LH production rate in fasting young men was accounted for by a 1.7-fold decline in the mass of LH secreted per burst (fed 2.5 +/- 0.45 vs. fasted 1.5 +/- 0.16 IU/L, P < 0.05), whereas LH burst mass in older men remained unchanged (and low) during fasting. In addition, in young men, during the 3.5-day fast the number of computer-resolved LH secretory bursts per 24 h decreased (fed 15 +/- 0.7 vs. fasted 11 +/- 0.7, P < 0.01), and the interburst interval increased (fed 94 +/- 4.2 vs. fasted 125 +/- 8.7 min, P < 0.05). In contrast, in older men in the fed state, basal LH peak frequency and serum free testosterone concentrations were reduced compared with corresponding values in young men, and did not decline further with fasting. Whereas the orderliness of LH release patterns increased significantly during fasting in the young men, the approximate entropy measure failed to change significantly in unfed older subjects. By cosinor analysis, young men showed lower 24-h mesor (mean of nyctohemeral rhythm of) serum LH concentrations than older volunteers during fasting. Moreover, young but not older men manifested preserved 24-h variations in LH interpulse intervals when fasting. Exogenously stimulated LH release (mean 3-h serum LH concentration or calculated mass of LH secreted) following a single i.v. injection of 10 micrograms GnRH was independent of age and fasting status. We conclude that the metabolic stressor of short-term fasting unmasks specific age-related neuroendocrine contrasts in the stress-responsive control of both the pulsatile and nyctohemeral regulation of the male hypothalamo-pituitary-gonadal-axis.

Chronic administration of the environmental pollutant 4-tert-octylphenol to adult male rats interferes with the secretion of luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone.

4-Tert-octylphenol (OP) is a prevalent environmental pollutant that has been shown to exert both toxic and estrogenic effects on mammalian cells. The effects of OP on the reproductive system of adult male vertebrates are virtually unknown. In the present study, we investigated the effects of chronic exposure to OP on reproductive hormone secretion in the adult male rat and compared the results qualitatively with those observed in other male rats treated chronically with estrogen. We injected corn oil vehicle or OP (20 or 80 mg) or estradiol valerate (EV; 0.8 or 8 microg) in oil s.c. into 2-mo-old male rats thrice weekly for either 1 or 2 mo. The 80-mg dosage of OP and one or both dosages of EV had the following effects: decreased anterior pituitary gland (APG) and serum LH and FSH concentrations; increased APG and serum prolactin (PRL) concentrations; increased APG/body weight ratios; decreased serum testosterone concentrations; decreased hematocrit; and decreased food consumption and body weight gain. To evaluate the response of the hypothalamus-APG to gonadal removal, we orchidectomized some of the rats after the end of treatment and decapitated them 3 wk later. In orchidectomized controls, serum LH and FSH concentrations rose markedly and serum PRL concentrations decreased. Similar changes were seen in orchidectomized rats treated previously with 20 or 80 mg OP. Moreover, there were no differences in mean serum LH, FSH, or PRL concentrations between controls and rats treated previously with either dosage of OP at 3 wk after orchidectomy. The results demonstrate that chronic administration of OP to adult male rats can adversely affect the secretion of reproductive hormones and strongly suggest that OP exerts these effects by acting like an estrogen. The opposite changes in LH, FSH, and PRL secretion observed after cessation of treatment with OP and orchidectomy suggest that chronic treatment with OP under the conditions of the present study did not result in any significant permanent deleterious effects on gonadotrophs or lactotrophs or the hypothalamic neurons controlling the secretion of the gonadotropins or PRL.

Assessment of development of the testes and accessory glands by ultrasonography in bull calves and associated endocrine changes

The testes, prostate and vesicular glands of 10 bull calves were examined by ultrasonography every 2 wk from 2 to 46 wk of age, at which time the scrotal circumference (SC) of all the calves had reached pubertal size (28 cms). Computer-assisted image intensity analysis (numerical pixel values) was conducted. Blood samples were collected every other week from 2 to 46 wk of age. Testicular diameter increased in a linear manner from 2 to 46 wk of age, but the diameter measured in a transverse plane (caudal) was greater between 10 and 34 wk of age than when measured in a longitudinal (lateral) plane (P<0 05). Growth of the prostate and vesicular glands, based on dimensions, was linear, but vesicular gland length increased more rapidly after 32 wk of age (P<0.05). Image intensity of the vesicular glands and prostate declined from birth or 8 wk of age, respectively, to 14 wk of age, increased to 18 wk and then declined to a nadir at 30 wk, followed by a rapid increase to 34 wk of age for the vesicular glands and to 46 wk of age for the prostate (P<0.05). Image intensity of the testes showed an early increase to 6 to 8 wk of age and a subsequent increase from about 20 wk of age to 46 wk of age, with an inflection at 30 wk of age (P<0.05). There was a transient increase in mean serum concentrations of LH between 6 and 20 wk of age (P<0.05), and LH concentrations appeared to increase again after 36 wk of age (P>0.05). Mean serum concentrations of FSH declined with age (P<0.05). Mean serum concentrations of testosterone increased after 32 wk of age (P<0.05) In summary, numerical pixel values comprising the ultrasound images of the developing testes, prostate and vesicular glands revealed a complex development pattern that may reflect important details of developmental stages.

Ultrasonography of the developing reproductive tract in ram lambs: Effects of a GnRH agonist

In spring-born ram lambs, the testes (from 2 wk), prostate and vesicular glands (from 4 wk) were examined by ultrasonography every 2 wk up to 26 wk of age. Image analysis was done (numerical pixel values). Ram lambs were treated with a long acting formulation of a GnRH superagonist (Leuprolide acetate; 1.5 mg/kg) at 3 and 7 wk of age. In blood samples taken every 15 min for 8 h, mean serum LH, LH pulse amplitude, and basal and mean serum FSH concentrations were lower at 5 wk of age, and LH pulse frequency was lower at 15 wk of age in animals given Leuprolide acetate compared with those of the controls. There were no differences (P>0.05) in testis, prostate or vesicular gland development between treated and control animals. Testicular diameter of the left and right testes in transverse and longitudinal planes increased slowly to 8 wk of age, more rapidly to 18 wk of age, then more slowly to 26 wk of age (P<0.05). Numerical pixel values of testicular images decreased from 2 to 8 wk of age, increased to 22 wk of age and then plateaued. Width of the prostate increased from 4 to 26 wk of age, but length and width of the vesicular glands increased slowly to 8 wk of age, more rapidly to 18 wk of age and then plateaued (P<0.05). Numerical pixel values for the prostate declined from 4 to 8 wk and for the vesicular glands, declined from 4 to 10 wk of age; numerical pixel values increased to 12 wk and then decreased to a nadir at 18 wk, followed by a steady increase to 26 wk of age (P<0.05). We concluded that developmental patterns of numerical pixel values of the testes, prostate and vesicular glands in ram lambs reflect stages of development, but treatment with a GnRH superagonist at 3 and 7 weeks of age did not affect growth of testes, vesicular or prostate glands