scholarly journals A Reevaluation of the Question: Is the Pubertal Resurgence in Pulsatile GnRH Release in the Male Rhesus Monkey (Macaca mulatta) Associated With a Gonad-Independent Augmentation of GH Secretion?

Endocrinology ◽  
2015 ◽  
Vol 156 (10) ◽  
pp. 3717-3724
Author(s):  
M. Shahab ◽  
M. Vargas Trujillo ◽  
T. M. Plant
Keyword(s):  
Repeated Measures ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Detection Algorithm ◽  
Juvenile Male ◽  
Gh Secretion ◽  
Pulsatile Gnrh ◽  
Gnrh Release ◽  
Somatic Signal ◽  
Lh Secretion

A somatic signal has been posited to trigger the pubertal resurgence in pulsatile GnRH secretion that initiates puberty in highly evolved primates. That GH might provide such a signal emerged in 2000 as a result of a study reporting that circulating nocturnal GH concentrations in castrated juvenile male monkeys increased in a 3-week period immediately preceding the pubertal resurgence of LH secretion. The present study was conducted to reexamine this intriguing relationship, again in an agonadal model. Four castrated juvenile male monkeys were implanted with indwelling jugular catheters, housed in remote sampling cages, and subjected to 24 hours of sequential blood sampling (every 30 min) every 2 weeks from 19.5 to 22 months of age. Twenty-four-hour profiles of circulating GH concentrations were analyzed using the pulse detection algorithm, PULSAR, and developmental changes in pulsatile GH release with respect to the initiation of the pubertal rise of LH secretion (week 0; observed between 22.5 and 32 mo of age) were examined for significance by a repeated-measures ANOVA. Changes in the parameters of pulsatile GH secretion, including mean 24-hour GH concentration and GH pulse frequency and pulse amplitude for 3 (n = 4) and 6 (n = 3) months before week 0 were unremarkable and nonsignificant. These findings fail to confirm those of the earlier study and lead us to conclude that the timing of the pubertal resurgence of GnRH release in the male monkey is not dictated by GH. Reasons for the discrepancy between the two studies are unclear.

Non-responsiveness of serum gonadotropins and testosterone to pulsatile GnRH in hemochromatosis suggesting a pituitary defect

1993 ◽  
Vol 128 (4) ◽  
pp. 351-354 ◽  
Author(s):  
Lise Duranteau ◽  
Philippe Chanson ◽  
Joelle Blumberg-Tick ◽  
Guy Thomas ◽  
Sylvie Brailly ◽  
...  
Keyword(s):  
Single Pulse ◽  
Serum Testosterone ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Gonadotropin Secretion ◽  
Pulsatile Gnrh ◽  
Serum Lh ◽  
Before And After ◽  
Gnrh Therapy ◽  
Lh Secretion

We investigated the potential pituitary origin of gonadal insufficiency in hemochromatosis. Gonadotropin secretion was studied in seven patients with hemochromatosis and hypogonadism, before and after chronic pulsatile GnRH therapy. Pulsatile LH secretion was studied before (sampling every 10 min for 6 h) and after 15-30 days of chronic pulsatile GnRH therapy (10-12 μg per pulse). Prior to GnRH therapy, all the patients had low serum testosterone, FSH and LH levels. LH secretion was non-pulsatile in four patients, while a single pulse was detected in the remaining three. Chronic pulsatile GnRH administration did not increase serum testosterone levels; similarly, serum LH levels remained low: neither pulse frequency nor pulse amplitude was modified. We conclude that hypogonadism in hemochromatosis is due to pituitary lesions.

scholarly journals Does Cortisol Inhibit Pulsatile Luteinizing Hormone Secretion at the Hypothalamic or Pituitary Level?

Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 692-698 ◽  
Author(s):  
Kellie M. Breen ◽  
Fred J. Karsch
Keyword(s):  
Plasma Cortisol ◽  
Hormone Secretion ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Luteinizing Hormone Secretion ◽  
Inflammatory Stress ◽  
Gnrh Secretion ◽  
Gnrh Release ◽  
Acute Increase ◽  
Lh Secretion

Abstract Elevations in glucocorticoids suppress pulsatile LH secretion in sheep, but the neuroendocrine sites and mechanisms of this disruption remain unclear. Here, we conducted two experiments in ovariectomized ewes to determine whether an acute increase in plasma cortisol inhibits pulsatile LH secretion by suppressing GnRH release into pituitary portal blood or by inhibiting pituitary responsiveness to GnRH. First, we sampled pituitary portal and peripheral blood after administration of cortisol to mimic the elevation stimulated by an immune/inflammatory stress. Within 1 h, cortisol inhibited LH pulse amplitude. LH pulse frequency, however, was unaffected. In contrast, cortisol did not suppress either parameter of GnRH secretion. Next, we assessed the effect of cortisol on pituitary responsiveness to exogenous GnRH pulses of fixed amplitude, duration, and frequency. Hourly pulses of GnRH were delivered to ewes in which endogenous GnRH secretion was blocked by estradiol. Cortisol, again, rapidly and robustly suppressed the amplitude of GnRH-induced LH pulses. We conclude that, in the ovariectomized ewe, cortisol suppresses pulsatile LH secretion by inhibiting pituitary responsiveness to GnRH rather than by suppressing hypothalamic GnRH release.

Pulsatile LH secretion in streptozotocin-induced diabetes in the rat

1991 ◽  
Vol 131 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Q. Dong ◽  
R. M. Lazarus ◽  
L. S. Wong ◽  
M. Vellios ◽  
D. J. Handelsman
Keyword(s):  
Weight Loss ◽  
Insulin Treatment ◽  
Pulse Generator ◽  
Latin Square ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Metabolic Effect ◽  
Male Rat ◽  
Free Access ◽  
Lh Secretion

ABSTRACT This study aimed to determine the effect of streptozotocin (STZ)-induced diabetes on pulsatile LH secretion in the mature male rat. LH pulse frequency was reduced by 56% and pulse amplitude by 54%, with a consequential decrease of 72% in mean LH levels 8 days after i.v. administration of STZ (55 mg/kg) to castrated Wistar rats compared with castrated non-diabetic controls. Twice daily insulin treatment completely reversed all parameters of pulsatile LH secretion to control values. Food-restricted non-diabetic controls, studied to distinguish the metabolic effect of diabetes from that of concurrent weight loss, demonstrated a 34% reduction in LH pulse frequency but no significant changes in LH pulse amplitude or mean LH levels compared with non-diabetic controls given free access to food. To distinguish whether the decreased LH pulse amplitude in diabetes was due to a reduction in either the quantity of hypothalamic gonadotrophin-releasing hormone (GnRH) released per secretory episode or to decreased pituitary responsiveness to GnRH, the responsiveness of the pituitary to exogenous GnRH (1–1000 ng/kg body weight) was tested in diabetic rats after castration, using a full Latin square experimental design. The net LH response (total area under response curve over 40 min following GnRH) was decreased by 33% (P=0·001) in diabetic compared with control rats. The decreased LH pulse frequency in STZ-induced diabetes therefore suggests that the metabolic effect of diabetes is to decelerate directly the firing rate of the hypothalamic GnRH pulse generator independent of testicular feed-back. These effects were fully reversed by insulin treatment and were only partly due to the associated weight loss. The impaired pituitary responsiveness to GnRH is at least partly involved in the reduction of LH pulse amplitude. Journal of Endocrinology (1991) 131, 49–55

scholarly journals The absence of corpus luteum formation alters the endocrine profile and affects follicular development during the first follicular wave in cattle

Reproduction ◽  
2008 ◽  
Vol 136 (6) ◽  
pp. 787-797 ◽  
Author(s):  
Ken-Go Hayashi ◽  
Motozumi Matsui ◽  
Takashi Shimizu ◽  
Natsuko Sudo ◽  
Ayako Sato ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Area Under The Curve ◽  
Follicular Development ◽  
Experimental Period ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Blood Collection ◽  
Gh Secretion ◽  
Endocrine Profile ◽  
Basal Concentration

We previously established a bovine experimental model showing that the corpus luteum (CL) does not appear following aspiration of the preovulatory follicle before the onset of LH surge. Using this model, the present study aimed to determine the profile of follicular development and the endocrinological environment in the absence of CL with variable nadir circulating progesterone (P4) concentrations during the oestrous cycle in cattle. Luteolysis was induced in heifers and cows and they were assigned either to have the dominant follicle aspirated (CL-absent) or ovulation induced (CL-present). Ultrasound scanning to observe the diameter of each follicle and blood collection was performed from the day of follicular aspiration or ovulation and continued for 6 days. The CL-absent cattle maintained nadir circulating P4throughout the experimental period and showed a similar diameter between the largest and second largest follicle, resulting in co-dominant follicles. Oestradiol (E2) concentrations were greater in the CL-absent cows than in the CL-present cows at day −1, day 1 and day 2 from follicular deviation. The CL-absent cows had a higher basal concentration, area under the curve (AUC), pulse amplitude and pulse frequency of LH than the CL-present cows. After follicular deviation, the CL-absent cows showed a greater basal concentration, AUC and pulse amplitude of growth hormone (GH) than the CL-present cows. These results suggest that the absence of CL accompanying nadir circulating P4induces an enhancement of LH pulses, which involves the growth of the co-dominant follicles. Our results also suggest that circulating levels of P4and E2affect pulsatile GH secretion in cattle.

Androgen negative feedback during the early rise in LH secretion in bull calves

1995 ◽  
Vol 145 (2) ◽  
pp. 243-249 ◽  
Author(s):  
N C Rawlings ◽  
A C O Evans
Keyword(s):  
Sexual Maturity ◽  
Initial Step ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Serum Samples ◽  
Bull Calf ◽  
Bull Calves ◽  
Early Increase ◽  
Early Rise ◽  
Lh Secretion

Abstract A transient elevation in mean circulating concentrations of LH and FSH occurs in the young bull calf prior to 24 weeks of age. The functional significance of this is not clear. To see if changes in the ability of androgens to suppress gonadotrophin secretion were involved in the start of this early rise in LH secretion or the cessation of the early rise in LH and FSH secretion, bull calves were treated with flutamide (androgen receptor blocker; n=5; 9 mg flutamide/kg body weight in propylene glycol (i.m./s.c.) in three equal portions at 12-h intervals) at 8, 16 and 24 weeks of age and bled every 15 min for 12 h beginning after the third flutamide treatment; control bulls received vehicle at these times. Control bulls (n=5) were bled every 15 min for 12 h at 4, 8, 12, 16 and 24 weeks of age, and all bulls were bled weekly. Serum samples were assayed for concentrations of LH, FSH and testosterone. Based on weekly and intensive bleedings for control and flutamide-treated bulls, an early rise in LH (8–18 weeks of age) and FSH (4–24 weeks of age) secretion was seen in all bull calves (P<0·05). At 8 weeks of age flutamide treatment resulted in increased mean serum LH concentrations (P<0·05); at 16 weeks of age it resulted in increased basal and mean LH concentrations and increased LH pulse frequency (P<0·05); and at 24 weeks of age in increased mean LH concentrations, LH pulse frequency and amplitude (P<0·05) in comparison with control bulls. Flutamide treatment resulted in decreased FSH pulse amplitude at 8 weeks of age and increased mean serum concentrations of FSH and FSH pulse frequency at 24 weeks of age (P<0·05). In flutamide-treated bull calves testicular growth was greater and sexual maturity was reached earlier than in control bull calves (P<0·05). We conclude that a reduced suppression of LH secretion by androgens does not appear to be a major contributing factor to the onset of the early increase in LH secretion, but increased suppression may be involved in the termination of the early rise of both LH and FSH secretion in the bull calf. The early increase in LH secretion may be a critical initial step in postnatal reproductive development, since flutamide treatment increased early LH secretion and resulted in earlier attainment of sexual maturity. Journal of Endocrinology (1995) 145, 243–249

scholarly journals Evidence that Orphanin FQ Mediates Progesterone Negative Feedback in the Ewe

Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4249-4258 ◽  
Author(s):  
Casey C Nestor ◽  
Lique M. Coolen ◽  
Gail L. Nesselrod ◽  
Miro Valent ◽  
John M. Connors ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Negative Feedback ◽  
Luteal Phase ◽  
Arcuate Nucleus ◽  
Pulse Amplitude ◽  
Estrogen Receptor Α ◽  
Pulse Frequency ◽  
Orphanin Fq ◽  
High Degree ◽  
Lh Secretion

Orphanin FQ (OFQ), a member of the opioid family, is found in many areas of the hypothalamus and, when given centrally OFQ inhibits episodic LH secretion in rodents and sheep. Because GnRH neurons are devoid of the appropriate receptors to mediate steroid negative feedback directly, neurons that release OFQ may be involved. Using immunocytochemistry, we first determined that most OFQ neurons in the arcuate nucleus (ARC) and other hypothalamic regions of luteal phase ewes contained both estrogen receptor α and progesterone (P) receptor. Given a similar high degree of steroid receptor colocalization in other ARC subpopulations, we examined whether OFQ neurons of the ARC contained those other neuropeptides and neurotransmitters. OFQ did not colocalize with kisspeptin, tyrosine hydroxylase, or agouti-related peptide, but all ARC OFQ neurons coexpressed proopiomelanocortin. To test for a role for endogenous OFQ, we examined the effects of an OFQ receptor antagonist, [Nphe1,Arg14,Lys15]Nociceptin-NH2 (UFP-101) (30 nmol intracerebroventricular/h), on LH secretion in steroid-treated ewes in the breeding season and ovary-intact ewes in anestrus. Ovariectomized ewes with luteal phase concentrations of P and estradiol showed a significant increase in LH pulse frequency during infusion of UFP-101 (4.5 ± 0.5 pulses/6 h) compared with saline infusion (2.6 ± 0.4 pulses/6 h), whereas ewes implanted with only estradiol did not. Ovary-intact anestrous ewes displayed no significant differences in LH pulse amplitude or frequency during infusion of UFP-101. Therefore, we conclude that OFQ mediates, at least in part, the negative feedback action of P on GnRH/LH pulse frequency in sheep.

Photoperiodic modulation of the dopaminergic control of pulsatile LH secretion in sheep

1994 ◽  
Vol 143 (1) ◽  
pp. 25-32 ◽  
Author(s):  
D J Tortonese ◽  
G A Lincoln
Keyword(s):  
Dopaminergic System ◽  
Pulse Frequency ◽  
Inhibitory System ◽  
Pulsatile Gnrh ◽  
Photoperiodic Regulation ◽  
Series Of Experiments ◽  
Induced Changes ◽  
Lh Secretion ◽  
Short Days ◽  
Sustained Increase

Abstract This study was conducted to investigate whether the photoperiodic regulation of the seasonal changes in pulsatile LH secretion in the ram involves changes in the activity of inhibitory hypothalamic dopaminergic (DA) pathways. To test this hypothesis, a series of experiments was carried out in Soay rams in which the effects of a DA-D2 receptor antagonist (sulpiride) or a DA-D2 receptor agonist (bromocriptine) on the pulsatile secretion of LH were determined under both long and short days. In each experiment blood samples were collected every 10 min for 8 h starting at the time of vehicle, sulpiride or bromocriptine injections to assess concentrations of LH. Sulpiride (0·59 mg/kg, s.c.) administered to rams under long days induced an immediate and sustained increase in the secretion of LH that lasted for approximately 4 h (P<0·05; ANOVA); this LH response reflected both a rise in mean concentrations (0·247 ± 0·03 vs.0·452 ± 0·1 μg/1) and an increase in the frequency of LH pulses (0·5±0·5 vs. 2·33±0·42 pulses/8 h; P<0·01). In contrast, under short days sulpiride had no effect. Bromocriptine (0·06 mg/kg, s.c.) administered to rams under long days, when LH concentrations were low, was without effect, but when given to rams under short days significantly (P<0·05) suppressed mean LH concentrations (0·627 ±0·08 vs. 0·320 ± 0·02 μg/l) and LH pulse frequency (4·86 ±0·46 vs. 2·43 ±0·37 pulses/8 h). In an additional experiment, pimozide (total dose: 0·16 mg/kg, i.m.), a DA antagonist less specific for DA-D2 receptors than sulpiride, was ineffective in modifying LH secretion in sexually inactive rams exposed to long days. These results are consistent with the hypothesis that an inhibitory dopaminergic system is involved in the regulation of pulsatile LH secretion in the ram. The induced changes in LH pulse frequency under long days (increased by sulpiride) and under short days (decreased by bromocriptine) indicate that, under both photoperiods, DA acts within the hypothalamus, via a specific DA-D2 receptor, to influence pulsatile GnRH secretion. A photoperiodic-induced activation of this inhibitory system may therefore represent the mechanism whereby long days suppress LH secretion and lead to the sexually inactive state characteristic of the non-breeding season. Journal of Endocrinology (1994) 143, 25–32

scholarly journals Gonadotropin-Inhibitory Hormone (GnIH) Secretion into the Ovine Hypophyseal Portal System

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3368-3375 ◽  
Author(s):  
Jeremy T. Smith ◽  
I. Ross Young ◽  
Johannes D. Veldhuis ◽  
Iain J. Clarke
Keyword(s):  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Portal Blood ◽  
Portal System ◽  
Dorsomedial Nucleus ◽  
Cellular Targets ◽  
Nonbreeding Season ◽  
Peripheral Blood Plasma ◽  
Gonadotropin Inhibitory Hormone ◽  
Lh Secretion

GnIH was first identified in avian species, and there is now strong evidence that it is operant in mammals as an inhibitor of reproduction. Mammalian gonadotropin-inhibitory hormone (GnIH)-3 is encoded by the RFRP gene in neurons of the dorsomedial nucleus. These neurons project to the median eminence, predicting a role as a secreted neurohormone and regulation of the pituitary gonadotropes. To determine whether GnIH-3 is a secreted neurohormone, we measured its concentration in hypophyseal portal blood in ewes during the nonbreeding (anestrous) season and during the luteal and follicular phases of the estrous cycle in the breeding season. Paired portal and jugular blood samples were collected and plasma prepared for RIA using an ovine GnIH-3 antibody. Pulsatile GnIH-3 secretion was observed in the portal blood of all animals. Mean GnIH-3 pulse amplitude and pulse frequency was higher during the nonbreeding season. GnIH-3 was virtually undetectable in peripheral blood plasma. There was a lack of association between secretory pulses of GnIH-3 (portal) and LH (peripheral). To determine the role of secreted GnIH-3, we examined its effects on GnRH-stimulated LH secretion in hypothalamo-pituitary-disconnected ewes; a significant reduction in the LH response to GnRH was observed. Finally, to identify cellular targets in the pituitary, the expression of GnIH receptor [G protein-coupled receptor 147 (GPR147)] in fractions enriched for gonadotropes somatotropes, and lactotropes was examined; expression was observed in each cell type. These data show GnIH-3 is secreted into portal blood to act on pituitary gonadotropes, reducing the action of GnRH.

3β-Hydroxysteroid dehydrogenase inhibitor reduces ovarian steroid production but increases ovulation rate in the ewe: interactions with gonadotrophins and inhibin

1992 ◽  
Vol 134 (1) ◽  
pp. 115-125 ◽  
Author(s):  
R. Webb ◽  
G. Baxter ◽  
D. McBride ◽  
A. S. McNeilly
Keyword(s):  
Detrimental Effect ◽  
Pulse Amplitude ◽  
Hydroxysteroid Dehydrogenase ◽  
Pulse Frequency ◽  
Oestrous Cycle ◽  
Ovulation Rate ◽  
Corpora Lutea ◽  
Lh Secretion ◽  
Higher Doses

ABSTRACT Two experiments were carried out during the breeding season in ewes, first to investigate the effects of oral administration of a 3β-hydroxysteroid dehydrogenase (3β-HSD) inhibitor (epostane) on the number of corpora lutea, and secondly to investigate the mechanism through which epostane acts. In the first experiment Dorset Horn ewes were treated orally with 25, 50, 100 or 200 mg epostane twice daily between days 10 and 15 of the oestrous cycle. All doses of epostane resulted in an increase in the number of corpora lutea per ewe, although the response was curvilinear, with the 25 mg dose showing the largest response and the 200 mg group the smallest response. Although there was no difference between groups in the number of ewes showing oestrus, the higher doses of epostane had a detrimental effect on fertility. In the second experiment Welsh Mountain ewes were treated twice daily with 25 mg epostane from day 10 of the oestrous cycle and the ovaries were removed for analysis during either the luteal or the follicular phases. Treatment significantly increased the number of follicles >6 mm in diameter, but significantly reduced in-vitro follicular oestradiol and testosterone production. Despite a marked increase in peripheral inhibin concentrations there was no effect on in-vitro inhibin production. Epostane treatment also caused a significant reduction in peripheral FSH concentrations and an increase in mean LH concentration. The latter was due to an increase in LH pulse frequency during the luteal phase and LH pulse amplitude during the follicular phase. These results confirm that treatment of ewes with epostane orally has a significant effect on follicular steroidogenesis and causes a significant increase in the number of corpora lutea per ewe. This effect on ovulation rate is not via an increase in peripheral FSH concentration, but may be caused by a reduction in follicular steroid activity either directly on the ovary or via an alteration in the pattern of LH secretion. Journal of Endocrinology (1992) 134, 115–125

scholarly journals Menopausal Increases in Pulsatile Gonadotropin-Releasing Hormone Release in a Nonhuman Primate (Macaca mulatta)

Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4653-4659 ◽  
Author(s):  
Andrea C. Gore ◽  
Bret M. Windsor-Engnell ◽  
Ei Terasawa
Keyword(s):  
Reproductive Function ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
Menopausal Transition ◽  
Primate Species ◽  
Primary Role ◽  
Pulsatile Gnrh ◽  
Direct Demonstration ◽  
Gnrh Release ◽  
Early Follicular Phase

Abstract Reproductive function in all vertebrates is controlled by the circhoral release of the neuropeptide, GnRH, into the portal capillary system leading to the anterior pituitary. Despite its primary role in sexual maturation and the maintenance of adult reproductive function, changes in the concentrations and pattern of GnRH release have not yet been reported in any primate species during the menopausal transition and postmenopause. Such knowledge is essential for ascertaining both the mechanisms for, and consequences of, the menopausal process. Here we used a push-pull perfusion method to measure and compare the parameters of pulsatile GnRH release in adult rhesus monkeys at 8.4 ± 1.5 yr (young adult females, early follicular phase, n = 6) and 28.8 ± 0.3 yr (aged females, n = 4, of which two monkeys were in the menopausal transition, and two were postmenopausal). Our results demonstrate that: 1) GnRH release is pulsatile in both young and aged monkeys; 2) mean concentrations of GnRH increase during reproductive aging; and 3) GnRH pulse frequency does not differ between aged monkeys and young monkeys in the early follicular phase. We conclude that not only do GnRH neurons have the continued capacity to release GnRH in a pulsatile manner but also they can do so with enhanced GnRH levels in aged primates. To our knowledge, this is the first direct demonstration of elevated pulsatile GnRH concentrations in a primate species during reproductive senescence, a result that may have implications for menopausal symptoms.

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