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 Pubertal Acceleration of Pulsatile Gonadotropin-Releasing Hormone Release in Male Rats as Revealed by Microdialysis

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 163-171 ◽  
Author(s):  
Glenn C. Harris ◽  
Jon E. Levine
Keyword(s):  
Vas Deferens ◽  
Pulse Generator ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Male Rats ◽  
Male Rat ◽  
Pubertal Maturation ◽  
Repeated Sampling ◽  
Generator Activity ◽  
Mature Spermatozoa

Abstract A microdialysis technique was used in male rats to directly assess the postulate that pubertal maturation is associated with accelerated GnRH pulsatility. Juvenile male rats, postnatal d 43 or 45 (n = 4) were stereotaxically fitted with guide cannulas directed toward the lateral median eminence, and repeated microdialysis experiments were conducted over 4–6 d. In each session, samples were collected continuously over 12 h (0900–2100 h) at 5-min intervals Results from individual peripubertal animals were pooled into two time bins for postnatal d 45–47 and 48–50, respectively, and GnRH characteristics were compared between the two epochs. The GnRH pulse frequency and mean GnRH concentration were significantly elevated at 48–50 d compared with 45–47 d. The GnRH pulsatility characteristics for 45–47 d vs. 48–50 d were as follows: pulse frequency, 0.74 ± 0.16 vs. 1.79 ± 0.19 pulses/h (P < 0.05); pulse amplitude, 254.1 ± 22.3 vs. 347.2 ± 15.8 Δpg/ml (difference in value from trough to peak); and mean release, 0.55 ± 0.03 vs. 2.04 ± 0.04 pg/5 min (P < 0.05). An additional two rats were dialyzed only once on postnatal d 50 to assess the effects of repeated sampling; the GnRH pulse characteristics in these animals were similar to those in rats sampled for a third or fourth time on postnatal d 48–50. To further assess the possible effects of repeated sampling on GnRH release profiles, a group of adult male rats (postnatal d 95–105; n = 3) was also dialyzed on four consecutive days. In these rats no significant alteration in GnRH pulse generator activity was observed over the four sessions. Moreover, the increase in GnRH pulse frequency observed in the peripubertal rats was found to be sustained in adult animals. To better understand the temporal relationship of GnRH pulse generator activity to reproductive maturation, groups of male rats were killed from postnatal d 45–56 along with an adult group at 95–105 d (n = 5/group) and examined for physiological signs of reproductive development. Gradual increases in serum levels of LH and testosterone and decreases in FSH and inhibin B were seen from postnatal d 45–56 to adulthood. Mature spermatozoa were found in the vas deferens by postnatal d 53. Our results demonstrate that in the late juvenile stage of male rat development, GnRH pulse generator activity is gradually accelerated over the course of consecutive days. This acceleration occurs over a period during which serum LH and testosterone are rising to adult levels, and it precedes the presence of mature spermatozoa in the vas deferens by 3 d. Our observations provide direct support for the hypothesis that an acceleration of GnRH pulsatility is the critical neural stimulus for the initiation of pubertal maturation in males. The peripheral and central cues that prompt the pubertal activation of the GnRH pulse generator remain to be characterized.

scholarly journals Accumulated Deep Sleep Is a Powerful Predictor of LH Pulse Onset in Pubertal Children

2015 ◽  
Vol 100 (3) ◽  
pp. 1062-1070 ◽  
Author(s):  
N. D. Shaw ◽  
J. P. Butler ◽  
S. Nemati ◽  
T. Kangarloo ◽  
M. Ghassemi ◽  
...  
Keyword(s):  
Pulse Generator ◽  
Average Length ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Sleep Fragmentation ◽  
Auditory Stimuli ◽  
Deep Sleep ◽  
Reproductive Axis ◽  
Clinical Research Center ◽  
Lh Secretion

Context: During puberty, reactivation of the reproductive axis occurs during sleep, with LH pulses specifically tied to deep sleep. This association suggests that deep sleep may stimulate LH secretion, but there have been no interventional studies to determine the characteristics of deep sleep required for LH pulse initiation. Objective: The objective of this study was to determine the effect of deep sleep fragmentation on LH secretion in pubertal children. Design and Setting: Studies were performed in a clinical research center. Subjects: Fourteen healthy pubertal children (11.3–14.1 y) participated in the study. Interventions: Subjects were randomized to two overnight studies with polysomnography and frequent blood sampling, with or without deep sleep disruption via auditory stimuli. Results: An average of 68.1 ±10.7 (± SE) auditory stimuli were delivered to interrupt deep sleep during the disruption night, limiting deep sleep to only brief episodes (average length disrupted 1.3 ± 0.2 min vs normal 7.1 ± 0.8 min, P < .001), and increasing the number of transitions between non-rapid eye movement (NREM), REM, and wake (disrupted 274.5 ± 33.4 vs normal 131.2 ± 8.1, P = .001). There were no differences in mean LH (normal: 3.2 ± 0.4 vs disrupted: 3.2 ± 0.5 IU/L), LH pulse frequency (0.6 ± 0.06 vs 0.6 ± 0.07 pulses/h), or LH pulse amplitude (2.8 ± 0.4 vs 2.8 ± 0.4 IU/L) between the two nights. Poisson process modeling demonstrated that the accumulation of deep sleep in the 20 minutes before an LH pulse, whether consolidated or fragmented, was a significant predictor of LH pulse onset (P < .001). Conclusion: In pubertal children, nocturnal LH augmentation and pulse patterning are resistant to deep sleep fragmentation. These data suggest that, even when fragmented, deep sleep is strongly related to activation of the GnRH pulse generator.

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 Neural Determinants of Pulsatile Luteinizing Hormone Secretion in Male Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Su Young Han ◽  
Isaiah Cheong ◽  
Tim McLennan ◽  
Allan E Herbison
Keyword(s):  
Luteinizing Hormone ◽  
High Frequency ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Frequency ◽  
Male Mice ◽  
Intact Male ◽  
Luteinizing Hormone Secretion ◽  
Pulse Profile ◽  
Lh Secretion

Abstract The gonadotrophin-releasing hormone (GnRH) pulse generator drives pulsatile luteinizing hormone (LH) secretion essential for fertility. However, the constraints within which the pulse generator operates to drive efficient LH pulsatility remain unclear. We used optogenetic activation of the arcuate nucleus kisspeptin neurons, recently identified as the GnRH pulse generator, to assess the efficiency of different pulse generator frequencies in driving pulsatile LH secretion in intact freely behaving male mice. Activating the pulse generator at 45-minute intervals generated LH pulses similar to those observed in intact male mice while 9-minute interval stimulation generated LH profiles indistinguishable from gonadectomized (GDX) male mice. However, more frequent activation of the pulse generator resulted in disordered LH secretion. Optogenetic experiments directly activating the distal projections of the GnRH neuron gave the exact same results, indicating the pituitary to be the locus of the high frequency decoding. To evaluate the state-dependent behavior of the pulse generator, the effects of high-frequency activation of the arcuate kisspeptin neurons were compared in GDX and intact mice. The same stimulus resulted in an overall inhibition of LH release in GDX mice but stimulation in intact males. These studies demonstrate that the GnRH pulse generator is the primary determinant of LH pulse profile and that a nonlinear relationship exists between pulse generator frequency and LH pulse frequency. This may underlie the ability of stimulatory inputs to the pulse generator to have opposite effects on LH secretion in intact and GDX animals.

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.

scholarly journals Suppression of the GnRH Pulse Generator by Neurokinin B Involves a κ-Opioid Receptor-Dependent Mechanism

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4894-4904 ◽  
Author(s):  
P. Grachev ◽  
X. F. Li ◽  
J. S. Kinsey-Jones ◽  
A. L. di Domenico ◽  
R. P. Millar ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Pulse Generator ◽  
Pulse Frequency ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Neurokinin B ◽  
Kndy Neurons ◽  
Lh Secretion ◽  
Dose Dependent

Abstract Neurokinin B (NKB) and its receptor (NK3R) are coexpressed with kisspeptin, Dynorphin A (Dyn), and their receptors [G-protein-coupled receptor-54 (GPR54)] and κ-opioid receptor (KOR), respectively] within kisspeptin/NKB/Dyn (KNDy) neurons in the hypothalamic arcuate nucleus (ARC), the proposed site of the GnRH pulse generator. Much previous research has employed intracerebroventricular (icv) administration of KNDy agonists and antagonists to address the functions of KNDy neurons. We performed a series of in vivo neuropharmacological experiments aiming to determine the role of NKB/NK3R signaling in modulating the GnRH pulse generator and elucidate the interaction between KNDy neuropeptide signaling systems, targeting our interventions to ARC KNDy neurons. First, we investigated the effect of intra-ARC administration of the selective NK3R agonist, senktide, on pulsatile LH secretion using a frequent automated serial sampling method to obtain blood samples from freely moving ovariectomized 17β-estradiol-replaced rats. Our results show that senktide suppresses LH pulses in a dose-dependent manner. Intra-ARC administration of U50488, a selective KOR agonist, also caused a dose-dependent, albeit more modest, decrease in LH pulse frequency. Thus we tested the hypothesis that Dyn/KOR signaling localized to the ARC mediates the senktide-induced suppression of the LH pulse by profiling pulsatile LH secretion in response to senktide in rats pretreated with nor-binaltorphimine, a selective KOR antagonist. We show that nor-binaltorphimine blocks the senktide-induced suppression of pulsatile LH secretion but does not affect LH pulse frequency per se. In order to address the effects of acute activation of ARC NK3R, we quantified (using quantitative RT-PCR) changes in mRNA levels of KNDy-associated genes in hypothalamic micropunches following intra-ARC administration of senktide. Senktide down-regulated expression of genes encoding GnRH and GPR54 (GNRH1 and Kiss1r, respectively), but did not affect the expression of Kiss1 (which encodes kisspeptin). We conclude that NKB suppresses the GnRH pulse generator in a KOR-dependent fashion and regulates gene expression in GnRH neurons.

scholarly journals Development of Gonadotropin-Releasing Hormone-1 Secretion in Mouse Nasal Explants

Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3221-3227 ◽  
Author(s):  
Stephanie Constantin ◽  
Alain Caraty ◽  
Susan Wray ◽  
Anne H. Duittoz
Keyword(s):  
Pulse Generator ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Early Developmental Stage ◽  
Limiting Factor ◽  
Sequence Of Events ◽  
Natural Ligands ◽  
Early Developmental ◽  
Secretory Pattern

Pulsatile release of GnRH-1 is critical to stimulate gonadotropes of the anterior pituitary. This secretory pattern seems to be inherent to GnRH-1 neurons, however, the mechanisms underlying such episodical release remain unknown. In monkey nasal explants, the GnRH-1 population exhibits synchronized calcium events with the same periodicity as GnRH-1 release, suggesting a link, though the sequence of events was unclear. GnRH-1 neurons in mouse nasal explants also exhibit synchronized calcium events. In the present work, GnRH-1 release was assayed in mouse nasal explants using radioimmunology and its relationship with calcium signaling analyzed. GnRH-1 neurons generated episodical release as early as 3 d in vitro (div) and maintained such release throughout the period studied (3–21 div). The pulse frequency remained constant, suggesting that the pulse generator is operative at an early developmental stage. In contrast, pulse amplitude increased 2-fold between 3 and 7 div, and again between 7 and 14 div, suggesting maturation in synthesizing and/or secretory mechanisms. To evaluate these possibilities, total GnRH-1 content was measured. Only a small increase in GnRH-1 content was detected between 7 and 14 div, whereas a large increase occurred between 14 and 21 div. These data indicate that GnRH-1 content was not a limiting factor for the amplitude of the pulses at 7 div but that the secretory mechanisms mature between 3 and 14 div. The application of kisspeptin-10 revealed the ability of GnRH-1 neurons to integrate signals from natural ligands into a secretory response. Finally, simultaneous sampling of medium and calcium imaging recordings indicated that the synchronized calcium events and secretory events are congruent.

scholarly journals Neonatal Lipopolysaccharide Exposure Exacerbates Stress-Induced Suppression of Luteinizing Hormone Pulse Frequency in Adulthood

Endocrinology ◽  
2007 ◽  
Vol 148 (12) ◽  
pp. 5984-5990 ◽  
Author(s):  
X. F. Li ◽  
J. S. Kinsey-Jones ◽  
A. M. I. Knox ◽  
X. Q. Wu ◽  
D. Tahsinsoy ◽  
...  
Keyword(s):  
Pulse Generator ◽  
Pulse Frequency ◽  
Inhibitory Influence ◽  
Adult Rats ◽  
Treatment Groups ◽  
Early Life Exposure ◽  
Stress Responsivity ◽  
17Β Estradiol ◽  
Lh Secretion

Early life exposure to immunological challenge has programming effects on the adult hypothalamo-pituitary-adrenocortical axis stress responsivity, and stress is known to suppress GnRH pulse generator activity, especially LH pulses. We investigated the effects of neonatal exposure to endotoxin on stress-induced suppression of pulsatile LH secretion and the involvement of corticotropin-releasing factor (CRF) receptor mechanisms in adult rats. Pups at 3 and 5 d of age were administered lipopolysaccharide (LPS, 50 μg/kg, ip). At 12 wk of age, they were ovariectomized and implanted with sc 17β-estradiol capsules and iv cannulas. Blood samples (25 μl) were collected every 5 min for 5 h for LH measurement. After 2 h of sampling, rats were given LPS (25 μg/kg, iv). CRF and CRF-R1 and CRF-R2 receptor mRNA was determined by RT-PCR in medial preoptic area (mPOA) micropunches collected at 3 h after LPS administration. There was no difference in basal LH pulse frequency between neonatal LPS- and neonatal saline-treated controls. However, neonatal endotoxin-treated rats exhibited a significantly greater LPS stress-induced suppression of LH pulse frequency. Basal mPOA CRF-R1 expression was unchanged in neonatal LPS- and neonatal saline-treated rats. However, CRF-R1 expression was significantly increased in response to LPS stress in neonatal LPS-treated animals but not in neonatal saline-treated controls. CRF and CRF-R2 expression was unchanged in all treatment groups. These data demonstrate that exposure to bacterial endotoxin in early neonatal life programs long-term sensitization of the GnRH pulse generator to the inhibitory influence of stress in adulthood, an effect that might involve up-regulation of CRF-R1 expression in the mPOA.

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.

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