Peak LH Levels Research Articles

γ-Aminobutyric Acid-A and -B Receptor Antagonists Increase Luteinizing Hormone-Releasing Hormone Neuronal Responsiveness to Intracerebroventricular Norepinephrine in Ovariectomized Estrogen-Treated Rats*

These studies determined whether endogenous gamma-aminobutyric acid (GABA) secretion affects LHRH neuronal responsiveness to norepinephrine (NE). The intracerebroventricular (icv) infusion of either bicuculline or phaclofen (GABA-A or GABA-B receptor antagonists, respectively) into ovariectomized (OVX) estrogen-treated rats did not affect basal LH levels (95 +/- 8.5 ng/ml) obtained over the 120 min of this study. When NE was infused icv, it produced a modest rise in plasma LH, which peaked within 15 min (240 +/- 25 ng/ml) and then declined toward baseline over the next 90 min. In contrast, if bicuculline was given icv at about time zero, and NE was infused (icv) 15 min later, plasma LH secretion was markedly increased and reached a peak concentration of 723 +/- 98 ng/ml within 15 min after NE treatment. Similarly, when bicuculline was infused into the medial preoptic area (MPOA), and NE was given 15 min later (icv), a peak LH level of 726 +/- 105 ng/ml was obtained within 15 min. If phaclofen was given icv at about time zero, and NE was infused 15 min later, LH rose dramatically to reach a peak concentration of 844 +/- 126 ng/ml within 15 min; a similar amplified LH response occurred when the GABA-B antagonist was infused into the MPOA and icv NE was given 15 min later. Comparisons of the LH responses obtained over the 120 min of the study suggest that icv infusions of the GABA-B receptor antagonist were more effective in sustaining peak LH secretion than the GABA-A receptor antagonist. In other groups of rats, the MPOA was electrochemically stimulated (ECS), and the effects of icv NE alone or combined with GABA receptor antagonists were evaluated. MPOA ECS alone induced a significant rise in plasma LH, which peaked between 35-45 min and then declined to approach basal levels by 150 min. In a second group, the MPOA was ECS, and at 30 min NE was infused icv. Plasma LH levels in these rats remained significantly elevated for the next 30 min before beginning their decline. In other animals, the MPOA was stimulated, and 15 min later either bicuculline or phaclofen was infused icv. Neither drug affected the patterns or concentrations of LH obtained after MPOA ECS alone. However, when rats received MPOA ECS plus either icv bicuculline or phaclofen, and these treatments were followed 15 min later by icv infusions of NE, LH secretion patterns and levels were altered significantly.(ABSTRACT TRUNCATED AT 400 WORDS)

Ovarian function during use of a levonorgestrel-releasing IUD

Ovarian function was studied for two complete menstrual cycles in 9 regularly menstruating women and for 8 weeks in three amenorrhoeic women who had used levonorgestrel-releasing IUDs (LNG-IUD) for more than four years. Nine patients using copper IUDs (Nova-T) were studied for two complete menstrual cycles as controls. According to progesterone levels, 15 17 cycles in women using LNG-IUDs were ovulatory, whereas only 8 17 cycles showed normal follicular growth and rupture as judged by ultrasound. In ovulatory cycles, the peak progesterone levels were lower than in the controls. The preovulatory estradiol and LH peak levels were also lower than in control subjects. SHBG levels were lower in LNG-IUD users than in copper IUD users. It is concluded that, although the dose of levonorgestrel released from the IUD is very low, it probably exerts an effect on the gonadotrophin secretion, which disturbs follicular development in many of the women studied, which in addition to the local effect on the endometrium, contributes to its high contraceptive efficacy.

EFFECTS OF BULL EXPOSURE ON POSTPARTUM INTERVAL AND REPRODUCTIVE PERFORMANCE IN BEEF COWS

One hundred and thirteen spring calving beef cows were utilized to study the effect of bull exposure during the early postpartum period on return to estrus and fertility. In the spring of 1985 and 1986, cows were randomly exposed to epididymectomized bulls (BE) 3–7 d after calving until beginning of the breeding season (n = 37, 1985; n = 20, 1986) or not exposed to bulls (NE) (n = 35, 1985; n = 21, 1986). Cows were observed for estrus twice daily beginning approximately 4 wk after the start of calving until synchronization. Estrous cycles of all cows were synchronized with Syncro-Mate B® (SMB) and cows inseminated 48 h after implant removal without regard to estrus. Calves were removed for 48 h following implant removal. Each year a group of cows was randomly selected from the BE group (n = 8, 1985; n = 7, 1986) and NE group (n = 8, 1985; n = 7, 1986) and cannulated at estrus after SMB implant removal. Blood samples were collected at 15-min intervals for 2 h and every 2 h for 46 h for determination of LH concentrations. Bull-exposed cows returned to estrus 16 d earlier (P < 0.01) than NE cows in 1985. In 1986, no difference was observed between BE and NE cows for days from calving to first estrus. The percentage of cows exhibiting estrus prior to synchronization was greater (P < 0.01) for BE cows than NE cows in 1985 (78 vs. 17%) and in 1986 (75 vs. 24%). Peak LH levels did not differ between treatment but were different between years. Time to the LH peak following SMB implant removal and calf removal did not differ between treatment and year. Conception rates were not influenced by bull exposure or year. Days from calving to conception were also not influenced by bull exposure. Key words: Bull exposure, cows, postpartum interval, reproduction

A Decrease in Opioid Tone Amplifies the Luteinizing Hormone Surge in Estrogen-Treated Ovariectomized Rats: Comparisons with Progesterone Effects*

It is well known that the estrogen-induced LH surge in ovariectomized (ovx) rats is invariably far less in magnitude than the preovulatory LH surge or that induced by progesterone (P) in estrogen-primed ovx rats. Recent studies show that a decrease in hypothalamic inhibitory opioid tone by the neural clock (NC) is responsible for the induction of the preovulatory LH surge on proestrus. Therefore, we hypothesized that the diminished LH response in estrogen-treated ovx rats may be due to an inadequate reduction in opioid tone. To test this hypothesis the effects of transiently decreasing the opioid tone with an opiate receptor antagonist, naloxone (NAL), on LH secretion in estrogen-primed, short term (5 days) and long term (4 weeks) ovx rats were examined. NAL (2 mg/h) was infused iv from 1100-1400 h on day 2 in rats receiving either sc implants (two, 15 mm each) filled with 17 beta-estradiol (300 micrograms/ml in oil) or sc estradiol benzoate (EB; 10 micrograms/rat) injections at 1000 h on day 0. For comparison of NAL- and P-induced LH responses, EB-primed short and long term ovx rats received P injection (2 mg/rat, sc) instead of NAL infusion at 1100 h. Estrogen treatment alone induced a spontaneous rise in plasma LH on the afternoon of day 2, with peak LH levels ranging between 1.5-2.4 ng/ml. NAL infusion markedly enhanced the LH surge in both groups of ovx rats. In short term ovx rats NAL-induced peak LH levels (5-6 ng/ml) were less than those observed in rats receiving supplemental P treatment or that observed previously on proestrus (10-15 ng/ml). However, in long term EB-primed ovx rats, NAL infusion evoked LH surges equivalent to those observed after P injection. In addition, analysis of the episodic LH secretion pattern showed that NAL infusion accelerated the frequency and amplitude of LH discharge and significantly changed the contour of LH episodes. These results show that a transient decrease in inhibitory opioid tone before a spontaneous LH rise in estrogen-treated ovx rats can accelerate episodic LH secretion to culminate in LH surges that resemble those induced by P and the preovulatory LH surge. Therefore, these observations are in accord with the view that the NC-induced curtailment in the inhibitory opioid tone may be inadequate in estrogen-treated rats; NAL infusion and P treatment intensify decrements in inhibitory opioid tone to reinstate the preovulatory-type LH surge in these rats.

Suppression of Gonadotropin Secretion by a Long-Acting Gonadotropin-Releasing Hormone Analog (Leuprolide Acetate, Lupron Depot) in Children with Precocious Puberty

The GnRH analog leuprolide acetate has been shown to be effective in the treatment of precocious puberty when given as a daily sc injection. We studied the effectiveness of a single im dose of a new depot form of leuprolide in suppressing estradiol and gonadotropin secretion in children with precocity. Five girls with previously untreated precocity showed significant decreases in basal serum estradiol and FSH levels and in peak LH levels (after GnRH testing) 30 days after a single im dose of leuprolide acetate for depot suspension. Mean peak FSH levels also fell greatly, but the difference was not significant. No adverse effects were noted during the first 4-6 months of monthly im injections. Depot im leuprolide appears to be effective in suppressing estradiol and gonadotropin secretion, and may be a useful method of treating children with central precocious puberty.

Gonadotropic stimulation of inhibin secretion by the human ovary during the follicular and early luteal phase of the cycle.

We studied the pattern of secretion of inhibin bioactivity from the ovary into peripheral blood during the follicular and early luteal phase of the menstrual cycle in women receiving gonadotropin therapy. Multiple follicular development was stimulated in 5 women undergoing in vitro fertilization and embryo transfer for tubal infertility using three different treatments designed to vary the concentration of FSH and LH (14 cycles). The women received clomiphene citrate (150 mg/day) from days 2-6 alone or supplemented with either exogenous human menopausal gonadotropin (28 IU/3 h) or pure FSH (28 IU/3 h) from day 6 until the day of follicle aspiration. Inhibin concentrations increased 10-fold in parallel with those of estradiol, from 0.2-0.3 U/mL on day 2 (before the onset of treatment) to 4-5 U/mL on day 14 of the cycle (time of the peak LH level). Coincidental to the LH surge, the inhibin concentration declined 2- to 3-fold before increasing again early in the luteal phase. The concentration of inhibin was higher in the gonadotropin-treated group (clomiphene plus human menopausal gonadotropin/FSH) than in the group treated with only clomiphene during the follicular phase. The number of follicles stimulated was significantly higher (P less than 0.001) in the group given exogenous gonadotropins [4.8 +/- 0.4 (SE)] than in the clomiphene alone group (2.2 +/- 0.4). These data strongly suggest that both the Graafian follicles and the corpus luteum secrete inhibin, which together with estradiol and progesterone may play a role in the regulation of FSH secretion during the luteal phase.

INCOMPLETE TESTICULAR FEMINIZATION WITH INCOMPLETE MULLERIAN REGRESSION

A 12 years old girl with clitoral hypertrophy, palpable testes in labia majora and prepubertal aspect of breast, pubic and axillary hair was evaluated. Her karyotype was 46 XY. Bone age was 9 years. Basal and peak FSH (34 and 104 mU/ml) and LH (10 and 49 mU/ml) were evaluated during a GnRH test. Testosterone levels (T), before and after HCG test (1000 U. I. every other day foi 5 days), were 27 and 208 ng/dl, respectively; basal Estradiol, 17OHP and Cortisol during ACTH test and TSH, T3 and T4 during TRH test were in the normal range. Genitography revealed the presence of rudimentary uterus with a right tube. Histologic examination of removed testes showed bilaterally normal prepubertal testes. Neither ovarian nor dysplastic tissue was found. Two months after surgery, basal and peak FSH (37 and 103 mU/ml) and LH (11 and 62 mU/ml) levels persisted elevated during GnRH test; T (<15 ng/dl) did not rise after HCG. This is the first report of incomplete testicular feminization with persistance of Mullerian structures probably due to a defective synthesis of MIF or some impairment of its action. Elevated FSH values, already reported in some cases of prepubertal TF, could be due to a decreased production of Inhibin.

Hormonal evaluation of boys born with undescended testes during their first year of life.

We studied pituitary-gonadal function during the first year of life in 48 boys born with 56 undescended testes in order to test the hypotheses that functional insufficiency of the hypothalamo-pituitary-gonadal axis and disorders of testosterone (T) biosynthesis occur in such boys. Cryptorchidism persisted for longer than 1 yr in 29 boys (30 testes; group I), whereas spontaneous descent occurred in 19 boys (20 testes; group II), in 6 after the sixth month. A control group (group III) included 160 boys. Basal and peak LHRH-stimulated serum LH and FSH and basal serum T values were determined at 3, 6, and 12 months. Serum T, dihydrotestosterone (DHT), progesterone (P), 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, and androstenedione before and after hCG administration were determined at age 1 yr. Comparing the 3 groups, cross-sectional evaluation revealed no significant differences in basal or peak LHRH-stimulated serum LH and FSH levels, except that basal serum LH levels were slightly higher in group II than in group III. Comparing groups I and II, longitudinal evaluation revealed similar basal and peak LHRH-stimulated serum LH and FSH values, with comparable changes with time. Basal serum T, DHT, and T precursor levels were similar in all three groups, with similar rises of T and DHT and variable minimal increases in androstenedione and dehydroepiandrosterone sulfate after hCG stimulation. We conclude that during the first year of life, boys with cryptorchidism have no functional insufficiency of the hypothalamo-pituitary-gonadal axis or disorders in T biosynthesis.

Influence of blindness on plasma luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone levels in prepubertal boys.

The aim of this study was to determine if changes in LH, FSH, PRL, and testosterone (T) secretion occur in blind prepubertal boys. Eight blind and six normal boys, aged 7-10 yr, living at an institute for blind subjects in Naples, Italy, were studied. Each had a combined GnRH (100 micrograms) and TRH (200 micrograms) test at 0800 h after nocturnal rest. Plasma LH, FSH, PRL, and T levels were measured by RIA. The blind boys had basal plasma LH, FSH, and T levels significantly lower than those in the normal boys (P less than 0.01 for all three); plasma PRL basal levels were similar to those in the normal boys. The blind boys, moreover, had lower peak LH, FSH, and PRL (P less than 0.01 for all three peaks) levels in response to GnRH-TRH. Our results, similar to those found by others in patients with delayed puberty or with hypogonadotropic hypogonadism, suggest that light stimuli influence neuroendocrine-gonadal activity in humans, as in other mammals; and in blind prepubertal boys, impaired hormone secretion could cause a delay of pubertal development or more severe hypogonadism.

DOSE-RELATED SUPPRESSION OF LH RESPONSE TO LHRH AND CLINICAL PARAMETERS BY NAFARELIN, AN INTRANASAL GnRH ANALOG

Twelve children (10 girls, 2 boys)with precocious puberty were treated with Nafarelin, an intranasal GnRH analog, for 6 months. Seven patients (mean age of 6.8 yrs) received 800 mcg and five patients (mean age of 7.8 yrs) received 1600 mcg daily at night. Standard LHRH tests were performed and secondary sex characteristics were assessed at 0, 3, and 6 months of therapy. Results are reported as mean ± SE.At 3 months of therapy the higher dose of nafarelin produced a significantly greater (p<.05) suppression of peak LH levels during the LHRH test. These differences were not significant by six months of therapy. Regression of breast development and reduction in pubic hair appeared to occur earlier in the children treated with the higher dose. These data suggest that the higher dose of Nafarelin may initiate a more rapid suppression of serum LH response and normalization of pubertl development. Follow-up studies are essential to determine if a more rapid decrease in LH will have a long-term impact on growth dynamics in children with precocious puberty.

Evidence that a decrease in opioid tone may evoke preovulatory luteinizing hormone release in the rat.

We have assessed the effects on LH release of prolonged naloxone (NAL) treatment before the critical period on proestrus. When LH secretion was monitored at 5-min intervals immediately after the start of continuous NAL infusion (2 mg/0.6 ml saline X h iv) at 1000 h, two types of responses were observed. In three of six rats, a small increase (1-2 ng rat LHRH-2/ml) during the first hour was followed by a sharp rise to 4-5 ng/ml in the second hour and a gradual return to baseline levels (0.5-1.00 ng/ml) in the third hour of infusion. In the remaining rats, LH responses were small with peak levels reaching 2 ng/ml range. When the effects were monitored 1 h after starting NAL infusion at 1000 h, the LH response was improved. Peak LH levels observed shortly before or after 1200 h varied between 4-14 ng/ml and in some rats the levels were comparable to those seen normally in the afternoon of proestrus (9-24 ng/ml). However, delaying the start of NAL infusion to 1200 h produced LH surges before 1400 h, with peak levels (27.5 +/- 5.5 ng/ml) in the range of normal preovulatory LH surges (peak levels 16.6 +/- 2.5 ng/ml), followed by a steady decrease in LH secretion. Additionally, sc NAL pellets implanted at 0930 h provoked premature LH hypersecretion with a temporal pattern (0930-1430 h) and magnitude (peak levels, 26.3 +/- 4.3 ng/ml between 1100-1200 h) comparable to the normal preovulatory LH surge observed after 1330 h. Since NAL is believed to antagonize the inhibitory effects of endogenous opioids on LH secretion, the results of this study imply that a sustained restraint on this inhibitory opioid tone can elicit the LH surge before the critical period on proestrus. These findings are in accord with our thesis that the neural clock that normally triggers the preovulatory LH surge may transiently decrease the inhibitory opioid tone to allow expression of crucial neural events which culminate in preovulatory LH secretion.

Influence of acute intracerebroventricular (i.c.v.) administration of adrenocorticotrophin (ACTH) on LH secretion in male rats: effect of pretreatment (i.c.v.) with ACTH antiserum on the serum LH response to an acute ether stress.

Adult male rats with chronic indwelling intracerebroventricular (i.c.v.) and jugular catheters were given an i.c.v. injection (over 1 min) of 1, 10, 100 ng or 1 microgram ACTH(1-24), or 300 ng ACTH(4-10) or saline, and blood samples were taken 0, 5, 15, 30 and 60 min later. Increasing dosages of ACTH(1-24) caused a dose-related rise in serum LH levels. Peak levels of serum LH (ranging from 157 to 473% of pretreatment levels) were reached 5-15 min after treatment, and then serum LH values returned to pretreatment levels by 60 min. The serum LH response to 1 microgram ACTH(1-24) did not differ from the response to 100 ng ACTH(1-24). Administration (i.c.v.) of 300 ng ACTH(4-10) was also effective in increasing serum LH values. Repeated withdrawal of blood during the experiment increased serum corticosterone values in all groups (including saline-treated), but i.c.v. administration of ACTH(1-24) or ACTH(4-10) did not further increase serum corticosterone levels. Two additional groups of rats were injected i.p. with either saline or pentobarbital (30 mg/kg body weight) 1 h before i.c.v. administration of 10 ng ACTH(1-24) and blood samples were taken as in the other groups. The animals in these groups did not show a rise in serum LH concentrations in response to ACTH(1-24). In a third experiment, rats were pretreated (i.c.v.) with either ACTH antiserum (ACTH-Ab) or normal rabbit serum 15 min before a 2-min ether stress. The ether stress evoked a significant rise in serum LH concentrations within 15 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Prolonged pulsatile administration of luteinizing hormone-releasing hormone in prepubertal children: diagnostic and physiologic aspects.

In order to test gonadotropic function 30 prepubertal and 2 early pubertal girls and boys were treated with LH-releasing hormone (LRH) in a pulsatile fashion for 7 days. LRH was administered iv either in a dose of 10 micrograms every 90 min or in a dose of 20 micrograms/1.73 m2 every 96 min. On days 1 and 7, just before as well as at the end of LRH treatment, a LRH test (100 micrograms/m2 iv) was performed. In 27 patients a LRH test was repeated 4 (day 11) or 7 days (day 14) after LRH withdrawal as well. Plasma LH, FSH, and estradiol or testosterone levels were estimated during the LRH tests on days 1, 7, and 11/14. The patients were divided into 4 groups: group 1 consisted of 2 girls and 1 boy with gonadal failure, group 2 of 1 girl and 2 boys with intact pituitary and gonadal function, group 3 of 11 girls and 13 boys with various central endocrine disorders, and group 4 of 1 girl and 1 boy with pubertal arrest of unknown origin. In group 1 LRH treatment elicited an increase of both gonadotropins into the castrate range, whereas gonadal steroids did not increase. In group 2 baseline LH as well as the response to LRH increased on day 7. In the boys FSH changed similarly. In the girl baseline FSH increased, but the high FSH response of day 1 decreased. Estradiol and testosterone levels were elevated on day 7. These changes during LRH treatment are similar to those during normal pubertal development. When the LRH test was repeated on day 11/14 basal levels had returned into the prepubertal range and a high response of LH especially was found in all 3 subjects. Patients of group 3 were separated into two subgroups: group 3a, those with, and group 3b, those without an increase of gonadal steroids on day 7 of LRH treatment. Since an increment must be the result of increased gonadotropin stimulation, this probably indicates intact gonadotropic function. Group 3a had a pattern of gonadotropin secretion similar to group 2. In group 3b basal and peak LH levels were lower on day 7 compared to group 3a, whereas FSH levels did not differ. Four or 7 days after LRH discontinuation (day 11/14) basal gonadotropin levels were in the original low range. In the LRH test mean LH peak level of group 3a was 43.7 U/liter, of group 3b 13.1 U/liter (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)

In vivo gonadotropin-releasing hormone release and serum luteinizing hormone measurements in ovariectomized, estrogen-treated rhesus macaques.

The push-pull perfusion technique was used to measure GnRH release in unanesthetized female rhesus macaques (Macaca mulatta) and to examine the dynamic relationship between GnRH release and LH levels during the estrogen-induced LH surge. Each ovariectomized macaque was anesthetized and stereotaxically fitted with a push-pull cannula directed into the median eminence (ME). After at least 1 week of recovery, each animal received an estradiol benzoate (E2B) injection (42 micrograms/kg BW) or an oil (OIL) injection and underwent push-pull perfusion of the ME and blood sampling for at least 5 h between 28 and 56 h postinjection. Continuous 10-min push-pull perfusates were collected and prepared for GnRH RIA. Peripheral venous blood samples were obtained either hourly or every 10 min, and serum LH levels were determined by Leydig cell bioassay. GnRH release was detectable and pulsatile in areas in or adjacent to the ME or arcuate nucleus. In eight OIL monkeys, GnRH pulses were regular (approximately one pulse every 60 min) and of low amplitude (14.7 +/- 12.0 pg), with a mean GnRH release rate of 4.0 +/- 1.7 pg/10 min. In five E2B-treated monkeys, GnRH release during the rising phase of the LH surge occurred as an apparent burst of high amplitude GnRH pulses. The mean GnRH release rate (37.5 +/- 17.9 pg/10 min) and mean GnRH pulse amplitude (170.0 +/- 90.0 pg) during the 5 h before the peak LH level in E2B-treated monkeys were greater than OIL values (P less than 0.025, mean release; P less than 0.05, mean amplitude). Within individual E2B-treated monkeys, hourly mean GnRH release rates were significantly correlated with LH levels during the ascending limb of the LH surge (r = 0.75 +/- 0.11; P less than 0.025). We have concluded that an increase in GnRH neurosecretion occurs in E2B-treated monkeys and that it is associated with generation of the LH surge. On the basis of our observations, we hypothesize that the primate hypothalamus, through changes in GnRH secretion, actively participates in the E2B-induced LH surge.

Differentiation of male hypogonadotropic hypogonadism and constitutional delay of puberty by pulsatile administration of gonadotropin-releasing hormone.

It is not possible to differentiate reliably between male idiopathic hypothalamic hypogonadism (HH) and severe constitutional delay of puberty (CD) on the basis of a standard GnRH bolus test (GBT) or other known endocrine or clinical parameters. Therefore, we studied the response of 17 hypogonadal men, 8 with a diagnosis of HH (age, 15.5-41; bone age, 12.5-19 yr; testes, 1-4 ml) and 9 with CD (age, 14.5-20; bone age, 11-15 yr, testes, 2-10 ml) to pulsatile GnRH stimulation. Basal and peak LH and FSH levels after a single dose of GnRH greatly overlapped between the two groups. In each patient, a spontaneous nocturnal plasma profile of LH and FSH, sampled every 20 min, was followed by a pulsatile GnRH stimulation (5 micrograms iv every 90 min) via a portable minipump for 36 h. Before and after this pulsatile GnRH stimulation, a GBT (60 micrograms/m2 iv) was performed and plasma LH, FSH, testosterone, androstenedione, and dehydroepiandrosterone sulfate were measured. Pulse analysis revealed 0-5 spontaneous nocturnal LH peaks in the CD patients but only one in all of the HH patients. During the 36 h of pulsatile GnRH, mean LH and FSH levels were significantly higher (P less than 0.0001) than during the spontaneous nocturnal profile in all patients (except 1 from each group for LH). The GBT after pulsatile stimulation caused significantly higher (P less than 0.001) LH increments in CD than in HH patients, with no overlap between the two groups (range, 4.1-15.6 in CD vs. 0.8-2.4 mIU/ml in HH). Plasma testosterone rose significantly (P less than 0.01) during pulsatile GnRH from 67 to 155 ng/dl (median) in the CD men, but did not change in the HH group (21 to 22.5 ng/dl). Plasma androstenedione and dehydroepiandrosterone sulfate did not rise in either group. We conclude that, in contrast to other parameters investigated so far, the LH increment in the second GBT after 36 h of pulsatile GnRH allows clear-cut differentiation between CD and HH. These results indicate significantly lower pituitary LH reserve in patients with permanent HH after short term priming of the pituitary by pulsatile GnRH administration.

Changes in luteinizing hormone-releasing hormone content of discrete hypothalamic areas associated with spontaneous and induced preovulatory luteinizing hormone surges in the domestic hen.

It is widely assumed that luteinizing hormone-releasing hormone (LHRH) neuronal activation is involved in the preovulatory surge of LH in the hen. In addition, this LH surge may be initiated by ovarian progesterone (P4) release. Thus, spontaneous and P4-induced LH surges should be associated with acute changes in LHRH content of discrete hypothalamic areas associated with LHRH cell bodies and/or LHRH axon terminals. Medial preoptic area (mPOA) and infundibulum (INF) LHRH content was measured by radioimmunoassay at intervals before, at, and following peak LH levels of a spontaneous preovulatory surge of LH, as well as when this surge was advanced by P4 administration in laying hens. Nonlaying birds served as additional controls. Levels of serum LH, P4, 17 beta-estradiol and pituitary LH were also measured. Increased (P less than 0.05) LHRH content in mPOA without changes in the INF are associated with peak serum LH levels of the spontaneous LH surge. By contrast, decreased (P less than 0.05) LHRH content in both mPOA and INF is associated with peak serum LH levels when the spontaneous surge was advanced 8 h by P4 administration to laying hens. Medial preoptic area and INF LHRH contents were significantly lower (P less than 0.05) in nonlaying than in laying hens.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of estradiol-17β and progesterone on serum levels of LH and FSH in the EWE before and after GnRH treatment

The interaction of estradiol and progesterone in controlling gonadotropin secretion was investigated in cyclic and anestrous ewes. The peak response of ewes to 200 ng of [D-Leu 6, des-Gly NH 2 10 proethylamide 9]-GnRH, in terms of serum LH concentrations, was greater on days 7 and 15 of the cycle (65.6 ± 23.60 ng/ml and 72.1 ± 14.82 ng/ml) than on days 2 and 11 (33.1 ± 11.12 ng/ml and 27.7 ± 6.3 ng/ml) (P<0.05). Peak FSH levels did not vary with the stage of the cycle (4.8 ± 0.25 ng/ml) (P>0.05). Using blank silastic rubber implants (no steroid) and various sizes of implants containing estradiol, serum estradiol concentrations of 20.6 ± 2.8 pg/ml, 33.0 ± 1.9 pg/ml, 37.7 ± 1.6 pg/ml, or 48.4 ± 1.8 pg/ml were produced in 4 groups of mid cycle ewes (days 7–9). Three of 5 ewes exhibiting the highest estradiol levels experienced a transient peak in serum concentrations of LH and FSH 24 ± 6 hr after implant insertion (LH 19.1 ± 3.84 ng/ml, FSH 34.3 ± 11.13 ng/ml). These 3 ewes subsequently underwent luteolysis. Estradiol treatment at mid cycle enhanced the response to the GnRH analog (P<0.05). Peak levels of LH and FSH after GnRH administration were 15.4 ± 4.66 ng/ml and 10.0 ± 3.93 ng/ml in control ewes; 44.0 ± 11.54 ng/ml and 32.4 ± 5.18 ng/ml in ewes treated with 1.5 × 0.24 cm implants; 26.3 ± 4.89 ng/ml and 23.0 ± 4.67 ng/ml in ewes treated with 3.0 × 0.24 cm implants; and 22.8 ± 4.99 ng/ml and 34.2 ± 8.87 ng/ml in ewes treated with 3.0 × 0.48 cm implants. Treatment of anestrous ewes (June) with progesterone, estradiol or progesterone and estradiol, depressed the peak response in serum FSH concentrations (6.2 ± 2.94 ng/ml) to the GnRH analogue as compared to ewes not given any steroid (16.3 ± 2.37 ng/ml) (P<0.05). The steroid treatments only depressed the LH response during the first hour after GnRH administration (P<0.05) (steroid treated ewes 5.7 ± 1.58 ng/ml, control ewes 18.4 ± 3.14 ng/ml). In conclusion, the response of serum levels of LH, but not FSH, to GnRH administration varied with the stage of the cycle and was influenced by both estradiol and progesterone. In anestrous ewes both steroids inhibited the response to GnRH. In general, a divergency in control mechanisms for LH and FSH is indicated.

Seasonal changes in circulating levels of luteinizing hormone and growth hormone in the migratory Canada goose

Seasonal changes in plasma levels of LH and GH in the Canada goose ( Branta canadensis interior) have been studied. The population examined breeds in the Canadian subarctic region (Fort Churchill, Manitoba) and winters in the southern United States (Swan Lake Refuge, Missouri). Peak levels of LH were observed during spring postmigratory (nest-building, early May) and nesting (incubating, early June) periods, while no significant differences were observed during the other periods studied. The highest levels of GH were observed during molting (late July) and the immediately following fall premigratory (early September) period.

Puberty in 24 patients with Klinefelter syndrome.

Twenty four boys with Klinefelter syndrome, 18 of whom were diagnosed prepubertally, were observed until adulthood. Onset of puberty, as judged from testicular enlargement and pubic hair development, occurred between 11 to 14 years in the above 18 patients. By the age of 17 pubic hair, penile length and height had reached the adult stage in all patients, but arrest of testicular growth was noted at midpuberty, 13 years, with maximal mean (±SD) volume attained being 3.5±1.5 ml. The first conscious ejaculation was reported to have occurred between 13 to 16 years in 10 patients and in the remaining 4 between 17 to 18 years of age. Sperm counts obtained after the age of 18 revealed azospermia or severe oligospermia in all patients except one, who had a sperm count of 30×106/ml. The hypothalamic-pituitary-gonadal axis, assessed by LH-RH and hCG stimulation tests, was found to be normal in prepuberty and during early pubertal stages. From mid-puberty the basal levels of plasma FSH and the response to LH-RH showed a gradual increase above the normal. Towards late puberty (>15 years) basal and peak levels of LH were above normal with a concomitant decrease in the basal level of testosterone and its response to hCG.

Temporal relationship of hormonal peaks to ovulation and sex skin deturgescence in the baboon

The purpose of this study was to determine the temporal relationship of peak levels of oestradiol (E2), LH and progesterone to ovulation and sex skin deturgescence in the baboon. A total of 55 baboons were used in these studies. Hormonal levels were measured in 47 cycles and ovulation was documented by laparoscopic examination in 26 of these cycles. A temporal relationship of ovulation to sex skin deturgescence was established in 57 cycles. The mean interval from E2 peak to ovulation was 41.4±2.3 hr, the interval from E2 peak to LH peak was 17.3±2.0 hr and that from LH peak to ovulation was 18.4±2.0 hr. Eleven baboons showed an LH peak on the day of the E2 peak. The number of days to the first sign of sex skin deturgescence after ovulation was 2.07±0.14 days (range 0–5 days). Nineteen cycles (33.3%) showed sex skin deturgescence 1 day after ovulation, another 19 cycles (33.3%) showed sex skin deturgescence 2 days after ovulation, and only 13 cycles (22.8%) showed sex skin deturgescence 3 days after ovulation. Sex skin deturgescence was observed on day 0, 4 or 5 postovulation in only two baboons.