FSH Response Research Articles

A Case of Pregnancy-induced Lymphocytic Adenohypophysitis Complicated by Postpartum Painless Thyroiditis

We report a patient with pregnancy-induced lymphocytic adenohypophysitis complicated by postpartum painless thyroiditis. A 27-year-old female noticed visual field defect in the 36th week of pregnancy. After delivery in the 39th week by cesarean section, she was admitted for close examination. Goiter was not palpable, and postpartum galactorrhea was not observed. Routine examination revealed no abnormal findings. On October 8, 1989, magnetic resonance imaging (MRI) revealed a tumor image (height 22.4mm) from the sella turcia to suprasellar cistern with a lower signal intensity than that of the white matter on T1 weighted images and a high signal intensity on T2 weighted images. Gd-DTPA contrast images showed a symmetrical and homogeneous tumor image at the same site. However, the posterior lobe of the pituitary gland appeared normal. These findings suggested lymphocytic adenohypophysitis. The LH was less than 0.3mIU/ml. The FSH (7.8mIU/ml), PRL (12ng/ml), GH (1.6ng/ml) and cortisol (10 micrograms/dl) levels were normal. T4 was 5.3 micrograms/dl, T3 67ng/dl, fT4 0.53ng/dl, which indicated mild hypothyroidism, but the TSH was normal. TRH test showed a slight increase in TSH and no response of PRL. Insulin tolerance test showed delayed response of GH and normal response of cortisol. LHRH test revealed no response of LH and delayed response of FSH. Anti-GH3 cell antibody and anti-thyroglobulin antibody were positive, but the anti-AtT20 cell antibody was negative. Since visual disturbance improved, and slight reduction in the mass (height 20.1mm) was confirmed by MRI after delivery on October 21, her course was observed without treatment. After 1 month, the LH became detectable, but the PRL and cortisol decreased to 2.5ng/ml and 6.0 micrograms/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Inhibitory Effects of 17β-Estradiol Are Observed on Gonadotropin Secretion from Perifused Pituitary Fragments of Metestrous, but Not Proestrous, Rats*

The in vivo suppression of LH by 17 beta-estradiol (E2) has been documented frequently. However, the demonstration of a direct inhibitory action of E2, in contrast to a stimulatory action, on the secretion of LH from the anterior pituitary has been inconsistent. The aim of this study was to determine if E2 can suppress either basal (unstimulated) or GnRH-stimulated gonadotropin secretion directly at the level of the anterior pituitary gland. Anterior pituitaries were obtained from metestrous and proestrous females rats at 0900 h, and trunk blood was collected for serum measurements of LH, FSH, E2, and progesterone (P). Each anterior pituitary was cut into eighths and placed into a microchamber for perifusion. Pituitary fragments were perifused at a rate of 10 ml/h using medium 199 (without phenol red) that contained E2 (1 nM) or ethanol as a control. Six pulses of GnRH (peak amplitude, 50 ng/ml; duration, 2 min) were administered one per h starting at 60 min. Fractions of perfusate were collected every 5 min for measurement of LH and FSH. The total amounts of LH and FSH secreted during the 1-h interval after each GnRH pulse or corresponding basal hour were calculated. Both basal and LH and FSH responses to GnRH were significantly greater from pituitaries of proestrous compared to metestrous rats. The selective suppression of LH secretion by in vitro treatment with E2 was demonstrated using pituitaries from metestrous rats receiving GnRH pulses, but not using pituitaries from proestrous rats. Thus, a negative feedback effect of E2 on LH secretion was observed only in pituitaries from donors with low serum levels of E2 and high P, but not from donors with high serum levels of E2 and low P. We believe that the in vivo steroid environment determined the subsequent responses to in vitro treatment with E2 on GnRH-stimulated gonadotropin secretion from the isolated pituitary gland.

Restoration of Normal Gonadotropin Responses to Naloxone by Chronic Bromocriptine Treatment in Elderly Men

Naloxone is unable to stimulate FSH and LH secretion in elderly men, suggesting a reduced endogenous opioid control of gonadotropin secretion in senescence. In the present study, we examined whether in elderly men a chronic dopaminergic stimulation with bromocriptine (5 mg/day for 7 days) modifies the gonadotropin response to naloxone (4 mg as an i.v. bolus plus 10 mg infused in 2 h). Eleven younger men (group 1, 22-40 years old) participated as controls. Twenty-two elderly men were selected from a larger population and were divided into two groups: subjects with compensated gonadal failure (normal blood testosterone and elevated gonadotropin concentrations; group 2, n = 11; 62-80 years old) and men with normal gonadal function (normal blood testosterone and gonadotropin levels; group 3, n = 11; 61-82 years old). Naloxone induced a striking LH and a slight but significant FSH increase in group 1, but was unable to change serum gonadotropin concentrations in elderly subjects of both groups 2 and 3. When experiments were repeated after bromocriptine treatment, no significant differences in LH and FSH responses to naloxone were observed in the younger subjects. On the other hand, bromocriptine restored significant gonadotropin responses to naloxone in elderly men. In fact, after bromocriptine, naloxone-induced FSH and LH increments in groups 2 and 3 were indistinguishable from those observed in group 1. These data suggest that in men age-related dopaminergic alterations may underlie the defective endogenous opioid control of gonadotropin secretion.

Plasma LH, FSH and testosterone concentrations in adult rams which were homozygous carriers or non-carriers of the Booroola fecundity gene

No gene-specific differences were found with respect to LH or testosterone pulsatile secretion (over 12 h), or in 12 hourly mean FSH concentrations in adult Booroola FF and ++ rams. Also, no differences between genotypes in the LH response to an injection of testosterone propionate, the FSH response to an infusion of bovine follicular fluid, or the testosterone response to injections of PMSG were noted. However, during the phase of seasonal testicular development, mean testosterone pulse amplitude (over 12 h) and the FSH response to 25 micrograms GnRH were higher in FF than in ++ rams (P less than 0.05); there were also significant effects of sire (P less than 0.05 in FF genotype only) and litter size (P less than 0.05) on testosterone pulse amplitude and GnRH-stimulated FSH release, respectively. During the breeding season, mean LH, but not FSH, concentrations were higher in FF than in ++ rams, after an injection of 0.5 micrograms GnRH; LH release was not affected by sire or litter size (P greater than 0.05). Long-term studies revealed that the FF rams were born in significantly larger litters, they weighed significantly less than ++ rams (P less than 0.05), and that bodyweight was significantly correlated (P less than 0.05) with litter size. There were no differences in testis size, and testis size was not significantly correlated with bodyweight. There was a strong tendency (P = 0.056) for overall mean FSH concentrations, measured weekly for 9 months, to be highest more often in FF than in ++ rams.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of Deslorelin Dose in the Treatment of Central Precocious Puberty

Central precocious puberty is effectively treated with long-acting LHRH analogs (LHRHas). Although at least six LHRHas have now been used in children, there have been no studies to determine the least effective dose of any of these analogs. We sought to determine the effect of decreasing an efficacious dose of deslorelin (D-Trp6-Pro9-NEt-LHRH) on basal and LHRH-stimulated gonadotropins, estradiol levels, and the rates of linear growth and skeletal maturation in subjects with central precocious puberty. Twenty-nine children with central precocious puberty were enrolled in a double blinded study. All subjects were treated for the initial 3 months with deslorelin at a dose (4 micrograms/kg.day, sc) known to suppress gonadotropins, linear growth velocity, and the rate of skeletal maturation. After 3 months, the subjects were randomly assigned to receive one of three daily sc doses of deslorelin: 4 micrograms/kg (n = 9), 2 micrograms/kg (n = 11), or 1 micrograms/kg (n = 9). They were treated at this dose in double blinded fashion for 15 months, after which time they resumed therapy at a dose of 4 micrograms/kg.day for an additional year. The children in the three groups did not differ in terms of chronological age, bone age, pretreatment growth rate, or Tanner stage at the onset of therapy. Similarly, there were no differences in the clinical and hormonal responses to the first 3 months of LHRHa therapy (4 micrograms/kg.day). During the 15-month period at the three different doses, the three dose groups could not be distinguished from each other in terms of pubertal stage, linear growth velocity, rate of skeletal maturation, sex steroid levels, mean LH or FSH levels, or peak FSH response to LHRH stimulation or to a dose of deslorelin. In contrast, the peak LH response to LHRH stimulation was highest in children treated with the lowest dose (1 micrograms/kg.day; P less than 0.025, by multiple analysis of variance). In addition, the peak LH response to a dose of deslorelin (the LHRHa test) was higher in children treated with 1 micrograms/kg.day than in those treated with 4 micrograms/kg.day (P less than 0.04). In summary, the LHRHa test is a sensitive means for detecting activation of the hypothalamic-pituitary-gonadal axis, and deslorelin at a dose of 1 micrograms/kg.day results in less gonadotropin suppression than a dose of 4 micrograms/kg.day.(ABSTRACT TRUNCATED AT 250 WORDS)

A Dose Finding Study of a Super Long-Acting Luteinizing Hormone-Releasing Hormone Analog (Leuprolide Acetate Depot, TAP-144-SR) in the Treatment of Central Precocious Puberty.

The effect of leuprolide acetate (D-Leu6-[des-Gly10-NH2]-LH-RH ethylamide acetate) for depot suspension (TAP-144-SR), a synthetic analog of luteinizing hormone-releasing hormone, was examined in three doses in 36 patients (34 girls, 2 boys) with central precocious puberty. TAP-144-SR was injected subcutaneously every four weeks for twelve weeks, and clinical symptoms and plasma and urinary levels of various hormones were followed every four weeks. Eleven girls given 10 micrograms/kg showed a significant decrease in peak plasma LH and FSH responses to LH-RH test, but basal plasma LH and FSH did not change significantly. In 13 patients (11 girls and 2 boys) given 30 micrograms/kg and 12 girls given 90 micrograms/kg, both basal and peak LH and FSH were significantly suppressed. Urinary excretion of LH decreased significantly in all groups except in the 10 micrograms/kg group. Urinary excretion of FSH did not change significantly in the 10 and 30 micrograms/kg groups, but it decreased significantly in the 90 micrograms/kg group. In girls, plasma and urinary estradiol also fell greatly, but the difference was insignificant except in the 90 micrograms/kg group. Regression of sexual characteristics was observed in almost half of the patients at the 12th week of the treatment. Side effects were minimal. A dose of more than 30 micrograms/kg of TAP-144-SR is effective in suppressing gonadotropins and causing improvement of clinical symptoms, and appears to be useful in treating children with central precocious puberty.

Impaired prolactin response to hyperthermia in heroin addicts

The response of PRL, FSH and LH to sauna-induced hyperthermia was examined in 8 male former heroin addicts (studied after 14-24 days of abstinence) and 8 age- and sex-matched control subjects. The basal levels of PRL tended to be higher in former drug users than in control subjects (p = 0.07). After sauna, there were no changes in the addict group, whereas a significant increase was observed in normal subjects (p less than 0.001). Baseline plasma LH and FSH levels were significantly lower in former drug users (p = 0.02), but no change was found after sauna in either group. These findings are consistent with the existence of a deficient adaptation to thermal stress in chronic drug users, even after a relatively short drug-free period.

Hypothalamic-Pituitary-Ovarian Function in Menstruating Women with Turner Syndrome (45,X)

The hypothalamic-pituitary-ovarian hormone secretion patterns were evaluated in two women with 45,X Turner syndrome, spontaneous sexual development, and monthly menstrual periods. Each women had serum gonadotropin and sex steroid determinations during two or more menstrual cycles. During the follicular phase of a menstrual cycle, both women received 100 micrograms gonadotropin-releasing hormone (GnRH) s.c., and serum LH and FSH responses were determined. In addition, one woman collected daily overnight urine specimens for 40 consecutive days, spanning two menstrual periods, for the measurement of LH, FSH, estriol, and free progesterone. The randomly measured hormone results showed low serum progesterone concentrations during luteal phases, consistent with the interpretation of anovulation or inadequate corpus luteum function. At the time of the GnRH stimulation tests, baseline serum FSH concentrations and FSH responses to GnRH were within normal limits, whereas baseline LH levels and LH responses to GnRH were low. The pituitary gonadotropin secretion patterns were more consistent with patterns seen during early puberty than in the perimenopausal state. This interpretation was further confirmed by the urinary excretion patterns of gonadotropins, which were not significantly elevated. Furthermore, the urinary hormone profiles revealed that, although the intermenstrual period was of normal length, the follicular phase was prolonged, with normal levels of LH, FSH, and estriol excreted. The menstrual cycle studied was ovulatory but had a short luteal phase. The hormone results indicated that the dysgenetic ovary of women with 45,X Turner syndrome is capable of producing sufficient quantities of sex steroids and other regulatory factors to maintain gonadotropin secretion patterns that are reminiscent of early puberty.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypogonadotropic hypogonadism in idiopathic hemochromatosis: evidence for combined hypothalamic and pituitary involvement

Hypogonadism is a common finding in idiopathic hemochromatosis. Most studies have localized the defect to either the pituitary gland or the testes. We describe a case with evidence that favors the likely concomitant involvement of the hypothalamus as a factor in the observed hypogonadism. A clinically hypogonadal male with hemochromatosis had a low testosterone concentration with inappropriately normal serum LH levels. Leydig cell function was intact, as demonstrated by a normal increase in serum testosterone following HCG administration. However, although the pituitary secretion of LH was normal in response to GnRH stimulation, clomiphene administration did not produce an increase in LH and FSH, suggesting that there was a defect in the hypothalamic GnRH response. Since the FSH and prolactin responses to stimulatory testing were inadequate, coexisting pituitary dysfunction was likely also present. We conclude that this man had hypogonadism with laboratory evidence for a combined defect in hypothalamic and pituitary function.

Inhibition of LHRH-induced LH and FSH release by gonadotrophin surge-attenuating factor (GnSAF) from human follicular fluid

It has been suggested that in superovulated women the endogenous LH surge is attenuated by a non-steroidal factor, called gonadotrophin surge-attenuating factor (GnSAF), which reduces gonadotrophin secretion in response to LHRH. To determine whether human follicular fluid (hFF) from superovulated women contains GnSAF activity, the secretion of LH and FSH by cultured sheep pituitaries was studied. After charcoal extraction of steroids, hFF was treated by heparin/Sepharose chromatography, which reversibly binds inhibin. The effects of whole hFF and the bound and unbound fractions on basal and LHRH-induced gonadotrophin secretion were then assessed. Steroid-free hFF significantly reduced basal FSH, but not basal LH, secretion, and significantly attenuated the LH and FSH responses to LHRH. The bound (inhibin) fraction significantly decreased both basal and LHRH-induced FSH secretion but did not affect LH release. The unbound fraction had no effect on basal LH or FSH secretion, but significantly attenuated LHRH-induced secretion of both LH and FSH. We conclude that the unbound fraction of hFF from superovulated women contains GnSAF. It has been demonstrated that GnSAF is a non-steroidal factor and its activity is distinct from that of inhibin.

Ontogeny of gonadotrophin receptors and gonadotrophin-stimulated cyclic AMP production in the neonatal rat ovary

The sequence of appearance of FSH and LH receptors, and response of cyclic AMP (cAMP) production to these hormones and cholera toxin, were studied in the fetal and neonatal rat ovary. Specific binding of radiolabelled human (h)FSH and chorionic gonadotrophin (CG) to ovarian homogenates was first detectable on day 7 of life. The content of FSH receptors per ovary increased tenfold between days 7 and 16, and that of LH receptors 27-fold. A significant response of cAMP production in vitro to FSH appeared on day 4 of life, but no significant effect of hCG on cAMP was achieved until day 7. In contrast, cholera toxin had a marked effect on cAMP production by day 17 of fetal life. Although both FSH and LH receptors were detectable in the neonatal rat ovary by day 7, the present findings indicate that the FSH responsiveness of the ovary appears earlier than that of LH. The post-receptor machinery of cAMP production is already functional in the fetal ovary as shown by the experiments with cholera toxin. The appearance of the receptor may therefore be the last link in the ontogeny of the gonadotrophin signal transduction system in the ovary. To study the hormone dependence of the appearance of gonadotrophin responsiveness, neonatal female rats were treated on days 1-6 or 1-9 of life with a potent gonadotrophin-releasing hormone antagonist, and killed on the following day. In both treatment groups, the pituitary LH and FSH contents were suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Gonadotropin Secretory Dynamics During Puberty in Normal Girls and Boys

To determine the most useful index of pubertal gonadotropin secretion we measured spontaneous LH and FSH levels every 20 min for 24 h and the LH and FSH responses to LHRH in a total of 37 girls and 30 boys representing each of the 5 stages of puberty. Mean 24-h LH and FSH levels rose significantly with increasing pubertal stage in both girls and boys. LH peak amplitude increased significantly with increasing pubertal stage for both sexes, whereas FSH peak amplitude did not. LH and FSH peaks were present throughout the 24-h period in all children, but the frequency did not change significantly with increasing pubertal stage. Mean gonadotropin levels, peak amplitudes, and peak frequencies tended to be higher at night from pubertal stages 1-4 of puberty. There were no significant sex differences in mean LH, LH peak amplitude, or LH peak frequency. The LHRH-stimulated peak LH to peak FSH ratio was greater in boys than girls during pubertal stages 1-3 and was less useful in distinguishing pubertal from prepubertal boys. For girls, the most accurate index of pubertal gonadotropin secretion was a LHRH-stimulated peak LH to peak FSH ratio greater than 0.66, which detected 96% of the pubertal girls with no false positives. For boys, the most accurate index was a maximum spontaneous nighttime LH level of 12 IU/L or more, which detected 90% of the pubertal boys with no false positives. We conclude that there are important sex differences in the gonadotropin responses to LHRH during puberty, and that criteria for the onset of pubertal gonadotropin secretion should be sex specific.

Ovarian stimulation in previous failures from in-vitro fertilization: distinction of two groups of poor responders

Forty-three patients who responded poorly to previous stimulation with clomiphene citrate (CC)/human menopausal gonadotrophin (HMG) for IVF were followed during 70 further cycles. Eighteen patients had a normal FSH response to CC in the previous cycle, while 25 had an abnormal FSH response. Three stimulation protocols were used: buserelin/HMG, CC/HMG and HMG only. No difference between the two groups was observed in the dose of HMG used for any stimulation protocol. More cycles were cancelled due to a poor response in the abnormal response group compared to the normal response group. In the completed cycles, the maximum oestradiol level and number of oocytes retrieved were lower in the abnormal response group compared to the normal response group. The total pregnancy rate per patient, including spontaneous conceptions during the study period, was lower in the abnormal response group compared to the normal response group, 4 versus 33%. We conclude that poor responders with an abnormal FSH response to CC have a latent ovarian failure with a low chance of success in further IVF attempts.

PROLACTINOMA IN PEDIATRIC AGE: A LONGITUDINAL FOLLOW-UP

Approximately 10-20% of the prolactinomas are recognized before age 20. However, there are few reports on their medium and long term follow-up. Thirteen patients (8♂, 9♀) aged 14,2 - 20 yr. (X̄ 16,5 yr) with prolactinoma were followed for 9 m-12 yr. Headaches, impairment of pubertal development, galactorrhea and visual field defects were the most common clinical findings. The responses of LH and FSH to LHRH among patients varied from normal, exaggerated or absent. THe TRH (TSH) test was normal in 8/9 cases and in 1 ♂ a primary concomitant hypothyroidism was reported. Serum PRL was elevated in all patients ranging 77-1150 ng/ml (X̄ 378±285). PRL response after TRH was inadequate (X̄ Δ MAX:25%). Radiologically, the patients were classified (Vezina and Sutton) in Gl: n=3 (♂); G2: n=5 (4♂, 1♀); G3: n=3 (1♂, 2♀) and G4: n=2 (♀). Eight patients (4♂, 4♀) were initially treated with surgery, 7 of them (3♂, 4♀) with a persistent hyperprolactinemia required Bromocriptine (BEC) after surgery. In 5 cases (4♂, 1♀) SEC constituted the primary treatment, but 1 ♂ with failure to BEC therapy needed transsphenoidal adenomectomy. Follow-up was possible in 11 patients. Among those who underwent surgery, 1 ♂ recovered gonadal function spontaneously and 5 cases (3 ♂, 2♀) required complementary medical treatment. Among those treated initially with BEC 1♂ recovered menses spontaneously, 1 ♂ needed progesterone therapy, 1 ♂ did not achieve normal PRL values after 9 m of treatment, the adolescent who required surgery had normal PRL levels without menses and the ♀ recovered gonadal function. In conclusion: - Basal PRL levels seem to be the most relevant element in hte diagnosis of prolactinomas.

The Role of Lh in the Autofeedback Inhibition of Lh and Fsh Secretion in Ovariectomized Rats

This study examined the role of exogenous LH in the autofeedback regulation of LH and FSH release in ovariectomized rats. The rats were implanted with third ventricular cannulae three weeks after ovariectomy and fitted with silastic jugular cannulae one week later. Baseline hormone levels were established on the day of experimentation in conscious, unrestrained animals. Thereafter, experimental animals received intraventricularly (IVT) either a 9 ug or 20 ug dose of a purified preparation of human (h)LH that did not crossreact in our rLH RIA. In response to 20 ug, but not 9 ug of LH, plasma levels of both LH and FSH were significantly reduced during the following one hour period compared to values in controls receiving buffer IVT. Administration of ovine (o)LH (6 ug, IVT), a preparation which crossreacts in the rLH RIA, significantly elevated plasma levels of detectable LH during the experimental period indicating that LH reaches the blood stream from the third ventricle and, thus, may effect endogenous hormone release at either the pituitary or hypothalamic levels. However, in animals preinjected with 9 or 20 ug of hLH IVT one hour earlier the surge of both LH and FSH in response to LHRH (25 ng iv) was not different from that in the buffer-injected controls receiving LHRH which indicates that pituitary responsiveness was not suppressed by the effective dose of hLH. The results of this study suggest that the inhibitory shortloop feedback of LH on endogenous LH and FSH secretion in ovariectomized rats occurs at the level of the hypothalamus.

A Comparative and Longitudinal Study on Endocrine Changes Related to Ovarian Function in Patients with Anorexia Nervosa

Screening of androgens and estrogens in blood and a GnRH test were performed in 20 female patients with anorexia nervosa and in 10 lean and 10 normal weight healthy control subjects. Both control groups had regular ovulatory menstrual cycles. The investigation was performed in the mid-follicular phase. Several variables showed significant differences between the groups; the levels of PRL, estrone, estradiol, progesterone, testosterone, androstenedione, and LH were lowest in the patients with anorexia nervosa. The lean control group showed intermediate values for progesterone, androstenedione, and, to a smaller extent, testosterone. The FSH response to GnRH was significantly higher in the patient group, corresponding to the pattern of late prepubertal girls. Ten patients were seen in a follow-up study. Five had resumption of the menstrual cycle, and the others still had amenorrhea. The two subgroups did not differ in either weight gain or the basal hormonal variables investigated. After weight gain an increased LH response to GnRH was observed in both subgroups. Patients who had resumption of the menstrual cycle showed a higher response of LH to GnRH, both before and after weight gain. The mean increase in LH after GnRH administration was significantly different between the two subgroups. The results suggest that the GnRH test may be useful to assess the stage of the disease and to predict the outcome, especially with regard to restoration of the menstrual cycle.

Effects of the synthetic glucocorticoid dexamethasone on reproductive function in the ewe

Glucocorticoids have been found to inhibit reproductive function in most domestic species studied but, in the ewe, preliminary reports suggest that glucocorticoids may have little or no effect. This study investigated the effects of the synthetic glucocorticoid dexamethasone on oestrus and ovulation rate in ewes during the breeding season and gonadotrophin secretion in the breeding and non-breeding seasons. In cyclic ewes, dexamethasone treatment at rates of up to 2 mg/day did not affect the natural or pregnant mare serum gonadotrophin-stimulated ovulation rate, or the timing and incidence of behavioural oestrus (P greater than 0.05). Dexamethasone administration (2 mg/day) had no effect on LH secretion or the plasma LH response to a 1 micrograms injection of gonadotrophin-releasing hormone (GnRH) in ovariectomized ewes in the breeding and non-breeding seasons, and did not compromise the inhibition of plasma LH levels during chronic treatment with oestrogen. Similarly, dexamethasone had no effect on plasma FSH concentrations, but significantly (P less than 0.05) reduced the plasma FSH response to a 1 micrograms GnRH injection during chronic negative treatment with oestrogen in ovariectomized ewes. Collectively, these data show that in these experiments dexamethasone did not significantly modify reproductive function in the ewe, a finding that is in contrast to that found in other domestic species.

LH and FSH response of Holstein heifers to fertirelin acetate, gonadorelin and buserelin

This study was conducted to describe the changes in serum LH and FSH concentrations in Holstein heifers following intramuscular (i.m.) injection of various dosages of fertirelin acetate and other commerically available GnRH products at their labeled dosages. The design was an incomplete Latin-square which gave nine replicates of each treatment. Treatments administered on Days 8 to 16 of the estrous cycle consisted of saline; 25, 50, 100 or 200 μg fertirelin acetate; 100, 250 or 500 μg gonadorelin; and 10 or 20 μg buserelin. Blood samples were collected via jugular catheters from 1 h before to 8 h after each injection. Log (Base 2) area under the LH and FSH curves (log AUC) were used to evaluate response to fertirelin acetate dosages and to determine difference (LSD: 0.05) and bioequivalence (α = 0.05) between the various dosages of GnRH products tested. Significant quadratic dose response relationships were detected for the LH and FSH log AUC data. Plots of the LH log AUC but not the FSH log AUC data suggested that a response plateau was being approached at the higher dosages of fertirelin acetate. Bioequivalence (α = 0.05) was based on the assumption that two means are equivalent if they differ by no more than 20% of the reference log AUC mean. Using these criteria fertirelin acetate is 2.5 to 10 times more potent than gonadorelin, whereas buserelin is approximately 10 to 20 times more potent than fertirelin acetate in the bovine for LH and FSH release.

Effect of naloxone on gonadotrophin secretion at various stages of development in the ewe lamb

Spring-born crossbred ewe lambs were raised in a natural photoperiod and saline (N = 6) or naloxone (1 mg/kg) in saline (N = 6) was injected (i.m.) every 2 h for 6 h at 5, 10 and 15 weeks of age and for 8 h at 20, 25 and 30 weeks of age. Blood samples were taken every 12 min during treatment periods. Naloxone had no effect on time to first oestrus (controls 235 +/- 6 days, naloxone 242 +/- 7 days). Mean serum LH concentrations and LH pulse frequency were elevated by naloxone in ewe lambs at 20, 25, and 30 weeks of age (P less than 0.05). The only FSH response to naloxone was a depression of mean serum concentrations at 30 weeks of age (P less than 0.05). LH pulse amplitude was elevated at 5 weeks of age in all ewe lambs and declined thereafter to a nadir at 30 weeks of age in control, but not in naloxone-treated animals (P less than 0.05). LH pulse frequency was elevated at 10 weeks of age in control ewe lambs and in all animals at 30 weeks of age (P less than 0.05). FSH pulse frequency declined from 5 weeks of age in control ewe lambs (P less than 0.05), with very few pulses noted in 25- and 30-week-old animals. We conclude that (1) opioidergic suppression of LH, but not FSH, secretion developed at 20 weeks of age in the growing ewe lambs used in the present study, with no obvious change in suppression before the onset of first oestrus: (2) pulsatile FSH secretion occurred in the young ewe lamb but was lost as the lamb matured: (3) attainment of sexual maturity was preceded by an elevation in LH pulse frequency.

Involvement of the adrenal gland in the suckling-induced decrease in LH and FSH secretion and the concomitant increase in prolactin secretion in the rat

The role of the adrenal gland in the regulation of gonadotrophin and prolactin secretion in the lactating rat was investigated. Changes in secretion of LH, FSH, prolactin, ACTH, beta-lipotrophin (beta-LPH), inhibin, corticosterone and progesterone after adrenalectomy were examined during the second half of lactation. Follicular maturation was determined by the ability of the follicles to ovulate in response to 10IU human chorionic gonadotrophin (hCG). Adrenalectomy on day 10 of lactation prevented an increase in plasma concentrations of LH and FSH in response to ovariectomy performed at the same time as adrenalectomy, and markedly stimulated secretion of ACTH, beta-LPH and prolactin. Adrenalectomy reduced the number of follicles capable of ovulating in response to hCG. Concentrations of inhibin and progesterone in the plasma significantly decreased after adrenalectomy, indicating that development of ovulatory follicles and luteal function had been suppressed. Abolishing the increase in plasma concentrations of LH and inducing a decrease in FSH in the plasma by adrenalectomy therefore prevented maturation of a new set of follicles usually seen during the second half of lactation in rats. The decrease in plasma concentrations of LH also inhibited the ability of the corpus luteum to secrete progesterone, although high concentrations of plasma prolactin were maintained in adrenalectomized lactating rats. These results indicate that the pituitary-adrenal system is capable of influencing the maintenance of a normal secretion of gonadotrophin and prolactin as well as the maintenance of ovarian function during lactation in the rat.