scholarly journals Central Infusion of Agouti-Related Peptide Suppresses Pulsatile Luteinizing Hormone Release in the Ovariectomized Rhesus Monkey

Endocrinology ◽  
2005 ◽  
Vol 146 (2) ◽  
pp. 784-789 ◽  
Author(s):  
Nicolas R. Vulliémoz ◽  
Ennian Xiao ◽  
Linna Xia-Zhang ◽  
Sharon L. Wardlaw ◽  
Michel Ferin
Keyword(s):  
Pulse Generator ◽  
Third Ventricle ◽  
Reproductive Function ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Melanocortin Receptor ◽  
Central Administration ◽  
Related Peptide ◽  
Orexigenic Peptide ◽  
Lh Release

Abstract Agouti-related peptide (AGRP), an endogenous melanocortin receptor antagonist, is a powerful orexigenic peptide when infused centrally. AGRP and neuropeptide Y (NPY), another orexigenic peptide, are colocated within the same neurons in the arcuate nucleus. Both NPY and AGRP mRNA expression increases during food restriction, a condition that is known to suppress the GnRH pulse generator and reproductive function. Although NPY has been shown previously to suppress LH secretion in the ovariectomized monkey, data on AGRP are lacking. In this study, we examined the effect of AGRP infusion into the third ventricle on pulsatile LH release in five adult monkeys. The 8-h protocol included a 3-h intraventricular saline infusion to establish baseline pulsatile LH release, followed by a 5-h infusion of AGRP (83–132) [5 μg/h (n = 1) or 10 μg/h (n = 4)]. In separate experiments, each animal received an 8-h saline treatment as a control. Blood samples were collected every 15 min for LH measurements. Cortisol levels were measured every 45 min. AGRP infusion significantly decreased LH pulse frequency (from a baseline of 0.74 ± 0.07 pulse/h to 0.36 ± 0.12 during AGRP infusion; P < 0.01) and mean LH concentrations (to 41.1 ± 7.5% of baseline by h 5 of AGRP infusion; P < 0.001). LH pulse amplitude was not modified by AGRP treatment. AGRP infusion also significantly increased cortisol release, as previously reported. The data demonstrate that central administration of AGRP inhibits pulsatile LH release in the monkey and suggest that AGRP, like NPY, may mediate the effect of a negative energy balance on the reproductive system by suppressing the GnRH pulse generator.

Changes in the characteristics of pulsatile luteinizing hormone secretion during the oestrous cycle and after ovariectomy and oestrogen treatment in female rats

1982 ◽  
Vol 94 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Takashi Higuchi ◽  
Masazumi Kawakami
Keyword(s):  
Hormone Secretion ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Oestrous Cycle ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Luteinizing Hormone Secretion ◽  
Oestrogen Treatment ◽  
Serum Lh ◽  
Lh Release

Changes in the characteristics of LH secretory pulses in female rats were determined in different hormonal conditions; during the oestrous cycle and after ovariectomy and oestrogen treatment. The frequency and amplitude of the LH pulses were stable during the oestrous cycle except at oestrus when a pattern could not be discerned because of low LH concentrations. These were significantly lower than those measured during other stages of the cycle. Mean LH concentrations and LH pulse amplitudes increased with time up to 30 days after ovariectomy. The frequency of the LH pulse was unchanged 4 days after ovariectomy when mean LH levels had already increased. The frequency increased 10 days after ovariectomy and then remained stable in spite of a further increase in mean serum LH concentrations. Oestradiol-17β injected into ovariectomized rats caused a decrease in LH pulse amplitude but no change in pulse frequency. One day after treatment with oestradiol benzoate no LH pulse was detectable, probably because the amplitude was too small. A generator of pulsatile LH release is postulated and an oestrogen effect on its function is discussed.

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.

Reproductive hormone secretion and spermatogenic function in thyroidectomized rams receiving graded doses of exogenous thyroxine

1986 ◽  
Vol 111 (2) ◽  
pp. 245-253 ◽  
Author(s):  
Y. Chandrasekhar ◽  
M. J. D'Occhio ◽  
B. P. Setchell
Keyword(s):  
Hormone Secretion ◽  
Reproductive Function ◽  
Pulse Frequency ◽  
Endocrine Function ◽  
Sex Hormone Binding Globulin ◽  
Testosterone Levels ◽  
Reproductive Endocrine ◽  
Lh Release ◽  
Lh Releasing Hormone ◽  
The Relationship

ABSTRACT This study aimed to obtain a better understanding of the relationship between circulating thyroxine (T4) concentrations and reproductive endocrine function in the ram. Mature Merino rams were thyroidectomized and supplemented with 0, 30, 100 and 300% of normal T4 for 10 weeks. Thyroidectomy had no apparent effect on spermatogenic function but interfered with sperm maturation, the latter being returned to normal by 30% T4 replacement. Circulating testosterone levels were reduced by thyroidectomy and restored to control levels by 30% T4; when T4 levels were supranormal (300%), circulating testosterone levels were again reduced. The lowered circulating testosterone levels in thyroidectomized rams occurred as a result of suppressed testosterone secretion from the testis, observed under basal conditions and also following LH-releasing hormone (LHRH) and human chorionic gonadotrophin injection. In thyroidectomized rams, sex hormone binding globulin (SHBG) levels were depressed without changes in testosterone clearance rate (TCR), while in rams with supranormal T4 levels, TCR was increased without changes in SHBG levels. Subnormal levels of T4 also restored to normal the reduced LH pulse frequency in thyroidectomized rams. Reduced LH pulse frequency, together with diminished LH release following LHRH injection in thyroidectomized rams, suggested effects of T4 at the hypothalamo-pituitary axis. The present study demonstrates that complete lack of thyroid hormones suppresses normal reproductive endocrine function in the ram, but that this can be restored to normal by 30% T4 replacement. The results support the theory that T4 plays a permissive rather than a regulatory role in reproductive function in males. J. Endocr. (1986) 111, 245–253

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 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 Effect of Continuous Intravenous Administration of Human Metastin 45–54 on the Neuroendocrine Activity of the Hypothalamic-Pituitary-Testicular Axis in the Adult Male Rhesus Monkey (Macaca mulatta)

Endocrinology ◽  
2007 ◽  
Vol 148 (7) ◽  
pp. 3364-3370 ◽  
Author(s):  
Suresh Ramaswamy ◽  
Stephanie B. Seminara ◽  
Clifford R. Pohl ◽  
Meloni J. DiPietro ◽  
William F. Crowley ◽  
...  
Keyword(s):  
Adult Male ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
High Dose ◽  
Continuous Exposure ◽  
Continuous Administration ◽  
Marked Rise ◽  
Lh Release ◽  
G Protein Coupled

In agonadal juvenile male monkeys, continuous administration of human metastin 45–54 (hu metastin 45–54) leads to desensitization of its receptor, G protein-coupled receptor 54 (GPR54), and decreased LH. The present study extended this observation to the adult male monkey, a more preclinically relevant model in which robust activity in the hypothalamic-pituitary-testicular axis is present. Continuous iv infusion of hu metastin 45–54 at either 200 or 400 μg/h elicited a marked rise in circulating LH that peaked 2–3 h after initiation of treatment. Thereafter, levels declined, and by 24 h, LH in metastin 45–54-infused animals was similar to control. LH release in response to an iv bolus of hu metastin 45–54 (10–30 μg) during the final 3 h of continuous infusion was truncated or abolished (low and high peptide dose, respectively). GPR54 desensitization by the high-dose metastin 45–54 infusion was associated with compromised pituitary response to a bolus GnRH injection (0.3 μg). LH pulse amplitude and pulse frequency were markedly suppressed during high-dose metastin 45–54 treatment. Surprisingly, the fidelity of the relationship between circulating testosterone (T) and LH was distorted during the high-dose peptide infusion. Thus, for a given concentration of LH, T levels were invariably higher during the high-dose metastin 45–54 infusion than during vehicle, suggesting that the peptide may exert direct actions on the testis to amplify T production. These findings support the notion that GPR54 is desensitized by continuous exposure to ligand, and they raise the possibility of an intratesticular role of GPR54.

Interaction of season and estradiol in the regulation of gonadotropin secretion in the adult ram

1990 ◽  
Vol 68 (2) ◽  
pp. 150-156 ◽  
Author(s):  
Lee M. Sanford ◽  
Bernard Robaire
Keyword(s):  
Follicle Stimulating Hormone ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Gonadotropin Releasing Hormone ◽  
Control Groups ◽  
Gonadotropin Secretion ◽  
Scrotal Circumference ◽  
Lh Release ◽  
Mean Concentration ◽  
Gonadotropic Hormones

The effects of season and estradiol on the secretion of gonadotropic hormones in adult Dorset × Leicester × Suffolk rams were studied. Control groups of intact and castrate rams, and castrate rams given estradiol replacement (~ 11.5 pg/mL) via polydimethylsiloxane capsules (sc) were assessed for 1 year, beginning in August. Mean concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were determined every 2 weeks for all three groups of rams and measurements of testosterone concentration and scrotal circumference were taken on the intact rams. Pulsatile LH release and the LH response to a 2-μg dose (iv) of gonadotropin-releasing hormone (GnRH) were assessed for all rams when the testes of intact rams were redeveloped (late October), regressed (early February, late April), and redeveloping (early August). Season directly affected LH-pulse amplitude, which increased only in the control castrate rams between February and April. In October, LH-pulse frequency was the same in both groups of castrate rams, while in April, frequency in the estradiol-treated castrate rams was suppressed to intact ram values. Pituitary responsiveness to exogenous GnRH did not change throughout the year in either of the castrate groups, but along with LH-pulse amplitude, it was increased in August in the intact rams. Although FSH secretion was 14-fold higher in the control castrate rams than in the intact rams, seasonal-directional changes in mean concentration were similar. FSH concentration in the estradiol-treated castrate rams was stable throughout the year. PRL secretion never differed between the control castrate and intact rams but was enhanced in the estradiol-treated castrate rams, particularly during long days.Key words: season, estradiol, gonadotropins, adult ram.

Role of RF-amid Related Peptide-3 (RFRP-3) in Inhibitory Effect of Orexin A on Reproductive Function in the Animal Model of Male Wistar Rats

2019 ◽  
Vol 127 (10) ◽  
pp. 697-705 ◽  
Author(s):  
Jafar Alipoor Hefshejanni ◽  
Homayoun Khazali
Keyword(s):  
Third Ventricle ◽  
Reproductive Function ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Orexin A ◽  
Hpg Axis ◽  
Related Peptide ◽  
Male Wistar Rats ◽  
Novel Target ◽  
The Impact

Abstract Aims The aim of the present study is to examine the orexin A (OXA) signaling can leave any impact on the hypothalamic-pituitary-gonadal (HPG) axis and this impact can be relayed through the pathway of RF amide-related peptide-3 (RFRP-3, the mammalian ortholog of the avian gonadotropin-inhibitory hormone)/G-protein coupled receptor (GPR)-147 (RFRP-3 receptor) as a novel target for controlling of HPG axis in the male rats. Materials and Methods Male rats were categorized randomly into experimental groups including control vehicle, OXA, and its antagonists’ group and went through to surgical cannulation into the third ventricle. After the intracerebroventricular injection of each solution, blood samples were collected for measurements of the LH and testosterone using radioimmunoassay method. Hypothalamus of the animals were isolated for analysis of the relative expression of Rfrp-3/Gpr-147 along with Gnrh gene by Real time-PCR. Also, in the different cohort of animal sexual behavior test was done. Results It was shown that OXA significantly decreases the mean serum level of the LH and testosterone and, at the same time, its antagonists neutralize this impact. Moreover, we demonstrated that OXA has reduced the hypothalamic gene expression of Gnrh and increased the expression of Rfrp-3 and Gpr-147 genes. While OXA antagonists neutralize this impact. Conclusions The results of this study are related to the impact of orexin on the HPG axis. It is recommended that RFRP-3/GPR-147 system as the interneural pathway relay the data of orexin to the neurons of GnRH.

Effect of epidermal growth factor on reproductive function of ewes

1985 ◽  
Vol 107 (3) ◽  
pp. 429-436 ◽  
Author(s):  
G. Shaw ◽  
G. I. Jorgensen ◽  
R. Tweedale ◽  
M. Tennison ◽  
M. J. Waters
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Luteal Phase ◽  
Reproductive Function ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Follicular Phase ◽  
Plasma Progesterone ◽  
Lh Surge ◽  
Epidermal Growth

ABSTRACT Adult Merino ewes were infused via the jugular vein with either saline (n = 5) or epidermal growth factor (EGF) (4·2 μg/kg per h, n = 6) for 24 h in either the luteal phase or the follicular phase of the oestrous cycle and reproductive function was examined. Infusion of EGF during the luteal phase caused no detectable change in plasma progesterone or prolactin concentrations over a 7-day period compared with the controls. Infusion of EGF during the follicular phase suppressed the oestrous rise in plasma oestradiol. Luteinizing hormone pulse amplitude was increased and pulse frequency was decreased by the end of the infusion. All control ewes had a pro-oestrous LH surge and mated, but the LH surge and oestrus were prevented by EGF infusion. Nevertheless, plasma progesterone levels rose subsequently in the EGF-infused ewes in parallel with the control ewes, suggesting that the preovulatory follicle had luteinized. Both LH and FSH rose over the 7 days after EGF infusion to levels similar to those in ovariectomized ewes. Thus EGF appears to inhibit follicular oestradiol production, although it does not affect luteal progesterone production or follicular luteinization. We suggest that the alteration in gonadotrophin secretion patterns results from a disturbance of feedback mechanisms between the ovary and the hypothalamopituitary axis, although a direct effect in the brain or the pituitary gland cannot yet be excluded. J. Endocr. (1985) 107, 429–436

LH pulsatility and in vitro bioactivity in women with anorexia nervosa-related hypothalamic amenorrhea

1991 ◽  
Vol 125 (6) ◽  
pp. 614-620 ◽  
Author(s):  
Jacques Allouche ◽  
Antoine Bennet ◽  
Pierre Barbe ◽  
Monique Plantavid ◽  
Philippe Caron ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Pulse Generator ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
In Vitro Bioactivity ◽  
Hypothalamic Amenorrhea ◽  
Blood Samples ◽  
Lh Pulsatility ◽  
Normal Women

Abstract. LH nocturnal pulsatility and bioactivity to immunoreactivity (B/I) ratio were determined in 16 patients with anorexia nervosa-related hypothalamic amenorrhea and low sex steroid levels, and in 12 normal women in the midfollicular phase. The patients were subdivided into 2 groups: IA (N=7) without, and IB (N=9) with documented recent weight gain. Blood samples were taken from each subject at 10-min intervals from 00.00 to 06.00 h. Immunoreactive LH data were analysed with cluster analysis algorithm. A pool of aliquots from all the samples was used to evaluate bioactive LH, immunoreactive LH and LH B/I ratio in each subject. LH pulse frequency was lower in Group IA than in controls, whereas it did not differ significantly between Group IB and controls. LH pulse amplitude was lower in Group IA, and higher in Group IB than in controls. LH B/I ratio was below the control range in 3/16 patients. In conclusion, persistent hypothalamic amenorrhea does not require a permanent inhibition of the GnRH pulse generator; transient inhibition of pulsatility and qualitative abnormalities of gonadotropins could be involved in the mechanism, at least in some patients.

Sign in / Sign up

Export Citation Format

Share Document