Pattern Of LH Secretion Research Articles

Effect of feed restriction during calfhood on serum concentrations of metabolic hormones, gonadotropins, testosterone, and on sexual development in bulls

The objective of the present study was to evaluate the effects offeed restriction during calfhood on serum concentrations of metabolic hormones, gonadotropins, and testosterone, and on sexual development in bulls. Eight beef bull calves received a control diet from 10 to 70 weeks of age. An additional 16 calves had restricted feed (75% of control) from 10 to 26 weeks of age (calfhood), followed by either control or high nutrition (n=8/group) during the peripubertal period until 70 weeks of age. Restricted feed during calfhood inhibited the hypothalamic GnRH pulse generator, reduced the pituitary response to GnRH, impaired testicular steroidogenesis, delayed puberty, and reduced testicular weight at 70 weeks of age, regardless of the nutrition during the peripubertal period. Restricted feed reduced serum IGF-I concentrations, but concentrations of leptin, insulin, and GH were not affected. In conclusion, restricted feed during calfhood impaired sexual development in bulls due to adverse effects on every level of the hypothalamus-pituitary-gonad axis and these effects were not overcome by supplemental feeding during the peripubertal period. Furthermore, based on temporal associations, the effects of restricted feed on the hypothalamus-pituitary-gonad axis might be mediated by serum IGF-I concentrations. These results supported the hypotheses that the pattern of LH secretion during the early gonadotropin rise during calfhood is the main determinant of age of puberty in bulls and that gonadotropin-independent mechanisms involved in testicular growth during the peripubertal period are affected by previous LH exposure.

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)

LH pulsatile release patterns, follicular growth and function during repetitive periods of suckling and non-suckling in sows

This paper presents LH, estradiol, and cortisol in 12 sows that were separated from their piglets for 12 h a day, beginning around 2 w of lactation, until weaning (intermittent suckling, IS). To separate sows from their piglets, the sows either were moved to a different unit (total separation), or were only inhibited from suckling their piglets by a physical barrier (physical separation). Blood samples were frequently collected during 4.5 consecutive days. At the start of IS, four sows showed advanced follicle growth. In the eight remaining sows, total separation resulted in 4/4 sows ovulating, while physical separation resulted in 2/4 sows ovulating. Total and physical separation resulted in different LH secretion patterns. Total separation resulted in a lower amplitude of LH pulses than physical separation throughout the period of sampling (0.26 versus 0.53 ng/ml; P < 0.01), and seemed to result in an escape from inhibition of LH secretion during suckling. Similarly, sows that ovulated had a lower amplitude of LH pulses (0.30 versus 0.54 ng/ml; P < 0.05), and also showed a different effect of suckling on LH secretion than anovulatory sows. Total separation, in contrast to physical separation, consistently resulted in increased cortisol after separation ( P < 0.05). This contrast was not observed between ovulating and non-ovulating sows. We therefore conclude that IS results in an increased LH secretion. Inhibition of all contact between sows and piglets seems to result in a more sustained increase in LH secretion, which increases the chance of ovulation.

Age or Factors Associated with Aging Attenuate Testosterone’s Concentration-Dependent Enhancement of the Regularity of Luteinizing Hormone Secretion in Healthy Men

Healthy older men have reduced testosterone (Te) production and frequent, small irregular LH pulses. Which is cause and which is effect are not known. In model systems, frequent and irregular LH pulses reflect attenuated feedback inhibition by Te. Factors associated with aging impair negative feedback by Te. Healthy men at an academic medical center were studied. The study used quantification of the regularity of LH release patterns during blockade of gonadal steroidogenesis and graded transdermal Te addback in 18 healthy men aged 18-65 yr. In the cohort as a whole, stepwise Te repletion repressed LH concentrations (P = 0.001) and enhanced the quantifiable orderliness of LH release patterns (P < 0.001). By regression analysis, age attenuated the capability of increasing Te concentrations to regularize LH secretion patterns (P = 0.019). However, after a fixed GnRH stimulus, the effect of Te on LH regularity was invariant of the age factor (P = 0.16), thus pointing to a hypothalamic locus of impaired Te feedback. Aging disrupts the capability of systemic Te concentrations to maintain orderly LH secretion under endogenous, but not exogenous, GnRH drive. Age or factors associated with increased age reduce negative feedback by any given total Te concentration on hypothalamopituitary GnRH-LH outflow, thus contributing to disorderly LH secretion.

Exogenous GH-releasing hormone increases GH and LH secretion in growing mithuns ( Bos frontalis)

To investigate the effects of growth hormone-releasing hormone (GHRH) administration on the patterns of GH and LH secretion in growing female mithuns, 12 mithuns within the age group of 10–12 months of age were divided into two groups (treatment and control groups) of six each in such a way that average body weight between the groups did not differ significantly ( P > 0.05). Both the groups were administered i.v. either with synthetic bGHRH [bGHRH (1-44)-NH 2] at 10 μg/100 kg body weight (treatment group) or equal volume of normal saline (control group). Blood samples collected prior to and after GHRH challenge at −60, −45, −30, −15, −10, −5 min and 5, 10, 15, 30 min, and thereafter, at an interval of 15 min up to 8 h post-injection were assayed for plasma GH and LH. Plasma progesterone was estimated in twice-a-week samples collected for six consecutive weeks preceding GHRH challenge to assess whether either group has begun ovarian cyclicity. Body weight of all animals was recorded once in a week during the period. A peak of GH was registered in all animals within 5–25 min post-GHRH administration with a mean peak of 443.5 ± 25.32 ng/ml at 15 min post-administration, which was much higher than in any other bovines reported following GHRH challenge. The patterns of LH secretion were pulsatile in nature in both the groups. Interestingly, the hormone concentrations exhibited higher pulsatility with greater amplitude after GHRH challenge in GHRH-treated than in control mithuns. The GHRH-treated mithuns averaged 0.44 pulses/h (4 pulses/9 h) and the rate was 0.20/h (2 pulses/9 h) in controls. The rate of pulse frequency and amplitude differed significantly with time of sampling. The mean plasma LH levels after GHRH administration were significantly higher in treatment group than those recorded in control mithuns. The mean plasma progesterone was similar ( P > 0.05) in both the groups and no animal from either group had begun ovarian cycle. In conclusion, exogenous GHRH significantly increases plasma GH and also LH pulse frequency and amplitude with higher mean post-GHRH LH levels in growing mithuns suggesting thereby its possible use for enhancement of maturity process in this unique meat animal.

Role of LH and prostaglandin F2α on the development and regression of corpus luteum in mithun ( Bos frontalis) estrous cycle

The present investigation was designed to study the role of LH and prostaglandin F2α (PGF2α) on the development and regression of corpus luteum (CL) in the mithun estrous cycle. Blood samples were collected from jugular vein and PGF2α secretion was evaluated on the basis of peripheral 15-keto-13,14-dihydro-PGF2α (PGFM) concentration. The daily variations in plasma LH, PGFM, and progesterone (P4) concentrations throughout the estrous cycle were monitored in morning and evening blood samples. The variations in plasma LH, PGFM, and P4 concentrations during the early luteal phase were monitored in blood samples that were collected every 2 h until 120 h following the onset of estrus (Day 0). The pulsatile secretion patterns of plasma LH, PGFM and P4 during estrus (Day1), mid-diestrus (Day 10), and luteolysis (Day 14) were assessed in blood samples that were collected every 15 min for 6 h. In the estrous cycle, P4 concentration increased above basal level on day 6–7, peaked on day 10–12 and declined thereafter. Following estrus, a significant ( P < 0.01) gradual increase in P4 concentration was observed. LH concentration was found to be significantly ( P < 0.01) greater around estrus and it declined gradually ( P < 0.01) following estrus. In the estrous cycle, PGFM concentration increased above basal level on day 9–11, peaked on day 16–17, and declined thereafter. The frequency of LH pulses and basal LH concentration were found to be significantly ( P < 0.01) greater on day 1, but significantly ( P < 0.01) greater amplitude of LH pulses was found on day 10 and 14. The frequency of P4 and PGFM pulses was found to be significantly ( P < 0.01) greater on day 1. In contrast, the amplitude of P4 and PGFM pulses and basal P4 and PGFM concentrations were found to be significantly ( P < 0.01) greater on day 10 and 14. The results indicate that probably the early stages of CL development continued until day 5–6 of the estrous cycle and a fully functional CL existed approximately at the mid estrous cycle. Luteolysis probably started since day 11–13 of the cycle and completed before the onset of the next estrus. The elevated basal LH concentration along with frequent low amplitude LH pulses were probably required for the early stages of CL development. In contrast, the high amplitude LH pulses of lower frequency during the mid estrous cycle were either sufficient or not required for maintaining the luteal function. Whereas, PGF2α pulses of greater amplitude and elevated basal PGF2α concentration during the mid and late estrous cycle were probably responsible for luteolysis.

Effects of the dopamine agonist cabergoline on the pulsatile and TRH-induced secretion of prolactin, LH, and testosterone in male beagle dogs

In the present study, the pulsatile serum profiles of prolactin, LH and testosterone were investigated in eight clinically healthy fertile male beagles of one to six years of age. Serum hormone concentrations were determined in blood samples collected at 15 min intervals over a period of 6 h before (control) and six days before the end of a four weeks treatment with the dopamine agonist cabergoline (5 μg kg −1 bodyweight/day). In addition, the effect of cabergoline administration was investigated on thyrotropin-releasing hormone (TRH)-induced changes in the serum concentrations of these hormones. In all eight dogs, the serum prolactin concentrations (mean 3.0 ± 0.3 ng ml −1) were on a relatively constant level not showing any pulsatility, while the secretion patterns of LH and testosterone were characterised by several hormone pulses. Cabergoline administration caused a minor but significant reduction of the mean prolactin concentration (2.9 ± 0.2 ng ml −1, p < 0.05) and did not affect the secretion of LH (mean 4.6 ± 1.3 ng ml −1 versus 4.4 ± 1.7 ng ml −1) or testosterone (2.5 ± 0.9 ng ml −1 versus 2.4 ± 1.2 ng ml −1). Under control conditions, a significant prolactin release was induced by intravenous TRH administration (before TRH: 3.8 ± 0.9 ng ml −1, 20 min after TRH: 9.1 ± 5.9 ng ml −1) demonstrating the role of TRH as potent prolactin releasing factor. This prolactin increase was almost completely suppressed under cabergoline medication (before TRH: 3.0 ± 0.2 ng ml −1, 20 min after TRH: 3.3 ± 0.5 ng ml −1). The concentrations of LH and testosterone were not affected by TRH administration. The results of these studies suggest that dopamine agonists mainly affect suprabasal secretion of prolactin in the dog.

Changes in circadian LH-secretion patterns and annual gonadal cycles in the male European starling (Sturnus vulgaris)

An analysis of the circadian and circannual patterns of luteinizing hormone (LH) secretion in male European starlings (Sturnus vulgaris) held in outdoor aviaries is presented. On the basis of six daily time points, eight calendar dates, and seven individuals per sampling unit, we present a mathematical model developed to compare the two temporal patterns of secretion, the circadian and the circannual one. The superposition of four orthonormal trigonometric base functions, plus a constant, is used to examine the daily fluctuations. The contribution of the second harmonic was not the same at each calendar date. From the subsequent regression functions, hourly estimates of LH concentration were calculated and used to construct circannual cubic splines and an LH(t,T) function over the whole year. The model features indicate strong circannual and circadian components in the data. In addition, there appear to be two daily time regions of LH secretion: morning and afternoon. In particular, the afternoon maxima occur during photorefractoriness and early gonadal development; the morning maxima at the onset of photoinduction and late gonadal development. At the peak of gonadal activity (end of April), the highest LH levels occur during the photic input phase. It appears, then, that the circadian acrophase of LH secretion in male starlings fluctuates over the annual cycle of gonadal activity in a highly predictive and biologically interpretable manner.

The effect of ram replacement and sex ratio on the sexual response of anoestrous ewes

It is accepted that an important source of variation in the response of anoestrous ewes, to the introduction of rams, is the intensity of male stimulation. The aim of this study was to investigate strategies capable of increasing the impact and transmission of the ram stimuli. In Experiment 1, two groups of seven ewes (Bluefaced Leicester♂ × Swaledale♀) were individually penned with one ram and for the next 6 h the rams either remained in the pen or were replaced hourly. Blood samples revealed no difference in the pattern of plasma LH secretion. In Experiment 2, three groups of 16 ewes were either introduced to one ram, individually (H) or in groups of 8 (L), or remained isolated. Ram introduction increased the plasma LH pulsatility ( P < 0.001). H ewes displayed more (nine versus six) male-induced LH pulses (pulses occurring within the first 45 min) and more pulses per 8 h intervals than the L group of ewes (1.9 ± 0.3 versus 1.3 ± 0.3), but these differences were not significant. It was concluded that (i) frequent replacement of rams within a few hours following ram introduction to ewes does not further improve the response of ewes, especially if the ram:ewe ratio is high; (ii) the characterization of the plasma LH secretion parameters during a period of 6–8 h does not seem to be an effective method to detect small differences in the intensity of stimulation received by the ewes when exposed to rams; (iii) North Country Mule ewes (Bluefaced Leicester♂ × Swaledale♀) in the UK respond to the presence of rams in spring (late oestrous/early anoestrous season) with an elevation in plasma LH secretion.

The temporal relationship between patterns of LH and FSH secretion, and development of ovulatory-sized follicles during the mid- to late-luteal phase of sheep

The aim of the present study was to investigate the temporal relationship between the secretory pattern of serum LH and FSH concentrations and waves of ovarian antral follicles during the luteal phase of the estrous cycle in sheep. The growth pattern of ovarian antral follicles and CL were monitored by transrectal ultrasonography and gonadotropin concentrations were measured in blood samples collected every 12 min for 6 h/d from 7 to 14 d after ovulation. There were two follicular waves (penultimate and final waves of the cycle) emerging and growing during the period of intensive blood sampling. Mean and basal LH concentrations and LH pulse frequency increased ( P < 0.001) with decreasing progesterone concentration at the end of the cycle. Mean and basal FSH concentrations reached a peak ( P < 0.01) on the day of follicular wave emergence before declining to a nadir by 2 d after emergence. None of the parameters of pulsatile LH secretion varied significantly with either the emergence of the final follicular wave or with the end of the growth phase of the largest follicle of the penultimate wave of the cycle. However, mean and basal LH concentrations did increase ( P < 0.05) after the end of the growth phase of the largest follicle of the final follicular wave of the cycle. Furthermore, the end of the growth phase of the largest follicle of the final wave coincided with functional luteolysis. In summary, there was no abrupt or short-term change in pulsatile LH secretion in association with the emergence or growth of the largest follicle of a wave. We concluded that the emergence and growth of ovarian antral follicles in follicular waves do not require changes in LH secretion, but may involve changes in sensitivity of ovarian follicles to serum LH concentrations.

Reversible Kallmann Syndrome, Delayed Puberty, and Isolated Anosmia Occurring in a Single Family with a Mutation in the Fibroblast Growth Factor Receptor 1 Gene

Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder. Recently, loss-of-function mutations in the fibroblast growth factor receptor 1 (FGFR1) gene have been shown to cause autosomal dominant KS. To date, the detailed reproductive phenotype of KS associated with mutations in the FGFR1 has yet to be described. We report a kindred comprising a male proband with KS and spontaneous reversibility, whose mother had delayed puberty and whose maternal grandfather isolated anosmia. The proband presented at age 18 yr with KS and was subsequently treated with testosterone (T) therapy. Upon discontinuation of T therapy, he recovered from his hypogonadotropic hypogonadism, as evidenced by a normal LH secretion pattern, sustained normal serum T levels, and active spermatogenesis. The three members of this single family harbor the same FGFR1 mutation (Arg(622)X) in the tyrosine kinase domain. This report demonstrates 1) the first genetic cause of the rare variant of reversible KS, 2) the reversal of hypogonadotropic hypogonadism in a proband carrying an FGFR1 mutation suggests a role of FGFR1 beyond embryonic GnRH neuron migration, and 3) a loss of function mutation in the FGFR1 gene causing delayed puberty.

Age and Testosterone Feedback Jointly Control the Dose-Dependent Actions of Gonadotropin-Releasing Hormone in Healthy Men

Healthy older men manifest combined declines in testosterone concentrations, LH secretory burst mass (amount of LH released per pulse), and feedback-sensitive regularity of unknown cause. To test a unifying hypothesis of simultaneous reductions in GnRH outflow, gonadotrope responsiveness to GnRH, and androgenic negative feedback, we monitored LH secretion 1) after bolus iv injection of a 1000-fold range of randomly ordered individual doses of GnRH on separate mornings, 2) during unmodified (eugonadal) or testosterone-withdrawn (hypoandrogenemic) negative feedback, and 3) in 16 young (age, 18-35 yr) and 15 older (age, 60-85 yr) healthy men. LH secretory burst mass and pattern regularity were quantitated by intensive blood sampling, high specificity LH beta-subunit-directed immunoradiometric assay, deconvolution analysis, and approximate entropy. GnRH dose responsiveness was assessed by four-parameter nonlinear regression analysis. We demonstrated that older men exhibit 1) delayed attainment of GnRH-evoked maximal LH secretion; 2) enhanced potency of GnRH stimulation in both the feedback-intact and feedback-withdrawn states; 3) elevated gonadotrope sensitivity to GnRH, unmasked by experimental testosterone depletion; 4) comparable young adult-like GnRH efficacy, independent of testosterone feedback milieu; and 5) diminished regularity of GnRH-induced LH release evident only during unmodified androgenic feedback. We conclude that a 3-fold interaction among GnRH dose, testosterone concentration, and age governs GnRH action, and age determines both testosterone-modulated and testosterone-independent actions of GnRH.

Glucoreceptors Located Inside the Blood-Brain Barrier Mediate Hypoglycemia-Induced LH Inhibition in Man

Objective: To establish the role of hyperinsulinemia and hypoglycemia during the insulin tolerance test (ITT) in the regulation of luteinizing hormone (LH) secretion and the location with respect to the blood-brain barrier (BBB) of the glucosensitive areas controlling LH release. Methods: The LH-secretory pattern during an ITT (0.15 IU/kg body weight) was evaluated in 8 normal men during infusion with normal saline (control test), glucose or fructose. Results: lnsulin-induced hypoglycemia produced a significant decrement in serum LH levels in the control test, but not when the concomitant infusion of glucose prevented hypoglycemia. Fructose infusion did not change LH decrease during ITT. Conclusions: These data exclude a direct role of hyperinsulinemia in the mechanism underlying the inhibition of LH secretion during ITT. Furthermore, since glucose but not fructose crosses the BBB, the LH decrease during ITT appears to be generated by hypoglycemia at the level of glucosensitive areas located inside the BBB.

Effects of long-term GH-releasing factor administration on patterns of GH and LH secretion in growing female buffaloes (Bubalus bubalis).

To investigate the effects of long-term GH-releasing factor (GRF) administration on the patterns of GH and LH secretion in growing female Murrah buffalo (Bubalus bubalis) calves, 12 buffaloes of 6-8 months of age were divided into two groups (treatment and control groups) of six each in such a way that average body weight between the groups did not differ significantly (P > 0.05). Both the groups were administered i.v. with either synthetic bovine GRF (bGRF(1-44)-NH(2)) at 10 microg/100 kg body weight (treatment group) or an equal volume of normal saline (control group) at intervals of 15 days until 18 injections had been completed (9 months). Blood samples collected prior to and after the first and last injection of GRF at -60, -45, -30, -15, -10, -5 min and +5, +10, +15, +30 min, and thereafter at intervals of 15 min up to 8 h post-injection, were assayed for plasma GH and LH. Plasma progesterone was also estimated in twice-a-week samples to assess whether either group had begun ovarian cyclicity. The body weight of all animals was recorded twice a week. In all animals, a peak of GH was recorded within 5-20 min and 5-30 min after the first and last GRF injections and post-injection mean values for plasma GH were significantly (P < 0.01) higher compared with the control group of animals. Although peak GH values after the first and last GRF injection did not differ (P > 0.05), GH levels were maintained at a higher level for a longer time after the last GRF injection compared with the first (240 vs 150 min). The area under the GH response curve after the last GRF injection was found to be significantly (P < 0.01) higher than after the first injection (9344 +/- 99.7 vs 7763 +/- 112.4 ng/ml x min). The mean post-injection plasma LH levels of the treatment group were significantly (P < 0.01) higher after both the first and last GRF injections than in the control group of animals. Interestingly, compared with the first GRF injection, the pre-injection plasma LH level was found to be significantly higher (P < 0.01) at the last injection. The plasma LH concentrations around the last injection of GRF were significantly higher (P < 0.01) than those recorded at the time of the first injection in treated buffaloes. Correspondingly, the plasma LH concentrations in controls were also higher (P < 0.01) around the last injection of GRF vis-à-vis the first injection. The hormone concentration exhibited a higher pulsatility with greater amplitude after the last injection as compared with that recorded after the first injection. Although pulses of LH were also recorded in controls following the last injection, these were fewer and of lower magnitude than those seen in treated animals. No animal from either group reached puberty. GRF-treated buffaloes attained higher (P < 0.001) body weight than the controls. In conclusion, long-term administration of GRF induces and even enhances GH release without any sign of refractoriness, and significantly increases plasma LH also. Hence, long-term treatment with GRF may be used to maintain a sustained increased level of plasma GH in buffaloes and it may assist the animals of this species to grow faster.

Effects of applying gamma-aminobutyric acid(B) drugs into the medial basal hypothalamus on basal luteinizing hormone concentrations and on luteinizing hormone surges in the female sheep.

Prior investigations have shown that localized infusion by microdialysis of gamma-aminobutyric acid(B) (GABA(B)) agonists into the medial basal hypothalamus of male sheep rapidly increases GnRH and LH pulse amplitude. The objectives of these studies were to determine if infusion of GABA(B) agonists SKF 97541 or baclofen into the medial basal hypothalamus of female sheep would affect basal LH secretion and if infusion of a potent antagonist would alter expression of LH surges induced by injection of estrogen. Infusion of either SKF 97541 (10 or 40 microM) or baclofen (1 mM) into estrogen-treated ovariectomized ewes did not alter basal LH secretory patterns, whereas both drugs significantly elevated mean LH and LH pulse amplitude in ovariectomized ewes during the nonbreeding season. Infusion of the antagonist CGP 52432 (250 or 500 microM) did not affect expression of estrogen-induced LH surges in ovariectomized ewes. These observations support the concept that GABA(B) receptors in the medial basal hypothalamus regulate basal LH secretion but do not regulate the surge mode of LH secretion in the female sheep.

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.

Chronic treatment with an agonist of gonadotropin-releasing hormone enhances luteal function in cattle.

Our hypothesis was that luteal function, as determined by plasma progesterone concentrations, and corpus luteum (CL) size is enhanced in cattle administered an agonist of GnRH when the CL is developing as compared with administration of an agonist when the CL is fully functional. Cattle were chronically administered a GnRH agonist, azagly-nafarelin, from Day 3 to Day 21 (D3) or Day 12 to Day 21 (D12) or served as untreated control females (Day 0 = behavioral estrus). Blood samples were serially collected on Days 7 and 14 to evaluate LH secretory patterns and twice daily to measure plasma progesterone. Ultrasonographic examinations were conducted daily to record the area of the CL. CL size and plasma progesterone concentrations were both enhanced in the D3 group as compared with the control group. Progesterone was increased in the D12 group on Days 16 and 17 as compared with the control females. Treatment with GnRH agonist increased basal and mean LH concentrations in both D3 and D12 groups as compared with the controls. We rejected our hypothesis because chronic administration of a GnRH agonist increased plasma progesterone when administered both when the CL was developing and when it was fully functional. The enhanced luteal function was likely due to increased basal LH.

Effects of pregnancy on pulsatile secretion of LH and gonadotrophin-releasing hormone-induced LH release in sheep: a longitudinal study

Pulsatile LH secretion and its control throughout pregnancy have not been fully determined in sheep. Expt 1 determined the patterns of LH secretion in five ewes on days 10, 20, 60 and 120 of pregnancy and on day 10 postpartum, compared with those on day 10 of the oestrous cycle. Mean (+/- SEM) concentrations of LH declined steadily throughout pregnancy (ANOVA, P < 0.01) and were lower (P < 0.01) on day 60 (0.19 +/- 0.3 ng ml(-1)) and on day 120 (0.18 +/- 0.4 ng ml(-1)) of pregnancy than on day 10 of the oestrous cycle (0.55 +/- 0.04 ng ml(-1)). This decrease was due to a significant reduction in the number and the amplitude of LH pulses. Only on day 120 of pregnancy were progesterone concentrations higher (P < 0.01) than on day 10 of the oestrous cycle. Although concentrations of progesterone on day 10 postpartum were barely detectable, mean LH concentration (0.45 +/- 0.09 ng ml(-1)) was not different from that on day 10 of the oestrous cycle. Expt 2 examined the LH responses in a separate group of four ewes to a physiological dose of GnRH (0.2 microg) on days 10, 20, 60 and 120 of pregnancy and on day 10 postpartum, compared with those on day 10 of the oestrous cycle. The area under the LH response curve and the maximum LH concentrations induced by GnRH declined steadily throughout pregnancy (ANOVA, P < 0.01) and were lower (P < 0.01) on days 60 and 120 of pregnancy than on day 10 of the oestrous cycle, but these parameters were not different between day 10 postpartum and day 10 of the oestrous cycle. Expt 3 examined the LH responses in a separate group of four ewes to a potent GnRH agonist, buserelin (0.5 microg), on days 10, 60 and 120 of pregnancy. The area under the LH response curve and the maximum LH concentrations induced by GnRH were lower (P < 0.01) on days 60 and 120 than on day 10 of pregnancy, but were not different between days 60 and 120. This longitudinal study demonstrates that the pulsatile LH release and pituitary responsiveness to GnRH decreases progressively as pregnancy advances, but does not support the hypothesis that high concentrations of progesterone are solely responsible for the inhibition of pulsatile LH secretion and GnRH-induced LH release during pregnancy in sheep.

Effects of pregnancy on pulsatile secretion of LH and gonadotrophin-releasing hormone-induced LH release in sheep: a longitudinal study

Pulsatile LH secretion and its control throughout pregnancy have not been fully determined in sheep. Expt 1 determined the patterns of LH secretion in five ewes on days 10, 20, 60 and 120 of pregnancy and on day 10 postpartum, compared with those on day 10 of the oestrous cycle. Mean (+/- SEM) concentrations of LH declined steadily throughout pregnancy (ANOVA, P < 0.01) and were lower (P < 0.01) on day 60 (0.19 +/- 0.3 ng ml(-1)) and on day 120 (0.18 +/- 0.4 ng ml(-1)) of pregnancy than on day 10 of the oestrous cycle (0.55 +/- 0.04 ng ml(-1)). This decrease was due to a significant reduction in the number and the amplitude of LH pulses. Only on day 120 of pregnancy were progesterone concentrations higher (P < 0.01) than on day 10 of the oestrous cycle. Although concentrations of progesterone on day 10 postpartum were barely detectable, mean LH concentration (0.45 +/- 0.09 ng ml(-1)) was not different from that on day 10 of the oestrous cycle. Expt 2 examined the LH responses in a separate group of four ewes to a physiological dose of GnRH (0.2 microg) on days 10, 20, 60 and 120 of pregnancy and on day 10 postpartum, compared with those on day 10 of the oestrous cycle. The area under the LH response curve and the maximum LH concentrations induced by GnRH declined steadily throughout pregnancy (ANOVA, P < 0.01) and were lower (P < 0.01) on days 60 and 120 of pregnancy than on day 10 of the oestrous cycle, but these parameters were not different between day 10 postpartum and day 10 of the oestrous cycle. Expt 3 examined the LH responses in a separate group of four ewes to a potent GnRH agonist, buserelin (0.5 microg), on days 10, 60 and 120 of pregnancy. The area under the LH response curve and the maximum LH concentrations induced by GnRH were lower (P < 0.01) on days 60 and 120 than on day 10 of pregnancy, but were not different between days 60 and 120. This longitudinal study demonstrates that the pulsatile LH release and pituitary responsiveness to GnRH decreases progressively as pregnancy advances, but does not support the hypothesis that high concentrations of progesterone are solely responsible for the inhibition of pulsatile LH secretion and GnRH-induced LH release during pregnancy in sheep.

Adrenal and gonadal function in obesity.

Obesity is associated with multiple alterations of the endocrine systems, including abnormal circulating blood hormone concentrations, due to changes in their pattern of secretion and/or metabolism, altered hormone transport, and/or action at the level of target tissues. There is evidence that alterations of endocrine systems regulating sex hormones and corticosteroids may play a crucial role in the development of obesity, particularly the abdominal phenotype. Obese women are characterized by a condition of sc"functional hyperandrogenism", whereas in males, obesity is associated with reduced T levels and decreased LH secretory pattern from the pituitary. In addition, in both sexes a dysregulation of the hypothalamic-pituitary-adrenal axis has been reported, including both neuroendocrine and peripheral alterations, finally leading to inappropriately higher than normal exposure to F of peripheral tissues, particularly the visceral adipose tissue. By these mechanisms, it can be hypothesized that both visceral fat enlargement and alterations of insulin action and associated metabolic disturbances may develop, therefore predisposing abdominally obese individuals to Type 2 diabetes and cardiovascular disease.