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.

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 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.

scholarly journals Blunted Day-Night Changes in Luteinizing Hormone Pulse Frequency in Girls With Obesity: the Potential Role of Hyperandrogenemia

2014 ◽  
Vol 99 (8) ◽  
pp. 2887-2896 ◽  
Author(s):  
Jessicah S. Collins ◽  
Jennifer P. Beller ◽  
Christine Burt Solorzano ◽  
James T. Patrie ◽  
R. Jeffrey Chang ◽  
...  
Keyword(s):  
Potential Role ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Cross Sectional ◽  
Obese Adolescent ◽  
Clinical Research Center ◽  
Obese Subjects ◽  
Sectional Analysis ◽  
Lh Secretion

Context: Puberty is marked by sleep-associated changes in LH pulse frequency and amplitude. Early pubertal girls with obesity exhibit blunted day-to-night changes in LH secretion; whether this occurs in late pubertal obese girls is unknown. Objective: The objective of the study was to test two hypotheses: 1) blunted day-to-night changes in LH secretion occur in both early and late pubertal obese girls, and 2) such alterations are specifically associated with hyperandrogenemia. Design: This was a cross-sectional analysis. Setting: The study was conducted at a clinical research center. Patients or Other Participants: Twenty-seven early pubertal, premenarcheal girls (12 of whom were obese) and 63 late pubertal (postmenarcheal) girls (27 of whom were obese) participated in the study. Intervention: Blood samples were taken every 10 minutes from 7:00 pm to 7:00 am. Main Outcome Measure: Change in LH pulse frequency [LH interpulse interval (IPI)] from daytime hours (7:00 pm-11:00 pm, while awake) to nighttime hours (11:00 pm to 7:00 am, while generally asleep). Results: Both nonobese and obese postmenarcheal girls demonstrated significant day-to-night decreases in LH pulse frequency (IPI increases of 33% and 16%, respectively), but day-to-night changes were blunted in obese girls (P = .004, obese vs nonobese). Day-to-night LH pulse frequency decreased significantly in postmenarcheal obese subjects with normal T concentrations (26% IPI increase) but not in those with hyperandrogenemia. Similar differences were evident for LH pulse amplitude. Nonobese and obese early pubertal girls exhibited nonsignificant differences in day-night LH pulse frequency (day to night IPI increase of 26% vs decrease of 1%, respectively). Conclusions: Day-to-night changes in LH pulse secretion are blunted in postmenarcheal obese adolescent girls. This phenomenon may in part reflect hyperandrogenemia.

Unaltered pulsatile and circadian TSH release in euthyroid patients with endemic goitre

1991 ◽  
Vol 124 (4) ◽  
pp. 386-390 ◽  
Author(s):  
Peter Weber ◽  
Ulrich Krause ◽  
Gabi Gaffga ◽  
Georg Brabant ◽  
Friedrich Manz ◽  
...  
Keyword(s):  
Thyroid Volume ◽  
Secretory Activity ◽  
Venous Catheter ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Pathophysiological Role ◽  
Tsh Secretion ◽  
The Mean ◽  
Serum Tsh

Abstract. To evaluate the pathophysiological role of TSH in goitrogenesis we investigated pulsatile TSH secretion in 11 patients with a non-toxic goitre and in 11 healthy controls. Thyroid volume was 40 ± 10 ml in the goitre group and 15 ± 4 ml in the controls as measured by ultrasound. Blood was sampled continously via an indwelling venous catheter at 10-min intervals over 24 h. Neither the mean 24-h serum TSH levels (goitre 1.1 ± 0.5 vs controls 0.9 ± 0.4 mU/l) nor the nocturnal surge of TSH were significantly different between the two groups. The average of the TSH pulse frequency (goitre 10.8 ± 3.7 vs controls 9.6 ± 3.5 pulses/24-h) and of the TSH pulse amplitude (goitre 0.4 ± 0.2 vs controls 0.3 ± 0.1 mU TSH/l as analysed by DESADE programme (detection of secretory activity by discrete deconvolution) did not differ in the two groups. Furthermore, there was no correlation between the volume of the thyroid gland and the dynamics of the TSH secretion. We conclude that our data do not suggest a relevant pathophysiological role of TSH secretion in the development of non-toxic goitre in man.

scholarly journals Developmental Increase in Kisspeptin-54 Release in Vivo Is Independent of the Pubertal Increase in Estradiol in Female Rhesus Monkeys (Macaca mulatta)

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1887-1897 ◽  
Author(s):  
Kathryn A. Guerriero ◽  
Kim L. Keen ◽  
Ei Terasawa
Keyword(s):  
Rhesus Monkeys ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Release Pattern ◽  
Female Rhesus ◽  
Gnrh Release ◽  
Important Regulator ◽  
Nocturnal Increase

Kisspeptin (KP) signaling has been proposed as an important regulator in the mechanism of puberty. In this study, to determine the role of KP in puberty, we assessed the in vivo release pattern of KP-54 from the basal hypothalamus/stalk-median eminence in prepubertal and pubertal ovarian-intact female rhesus monkeys. We found that there was a developmental increase in mean KP-54 release, pulse frequency, and pulse amplitude, which is parallel to the developmental changes in GnRH release that we previously reported. Moreover, a nocturnal increase in KP-54 release becomes prominent after the onset of puberty. Because the pubertal increase in GnRH release occurs independent of the pubertal increase in circulating gonadal steroids, we further examined whether ovariectomy (OVX) modifies the release pattern of KP-54. Results show that OVX in pubertal monkeys enhanced mean KP-54 release and pulse amplitude but not pulse frequency, whereas OVX did not alter the release pattern of KP-54 in prepubertal monkeys. Estradiol replacement in OVX pubertal monkeys suppressed mean KP-54 release and pulse amplitude but not pulse frequency. Estradiol replacement in OVX prepubertal monkeys did not alter the KP-54 release pattern. Collectively these results suggest that the pubertal increase in KP release occurs independent of the pubertal increase in circulating estradiol. Nevertheless, the pubertal increase in KP release is not likely responsible for the initiation of the pubertal increase in GnRH release. Rather, after puberty onset, the increase in KP release contributes to further increase GnRH release during the progression of puberty.

Effect of adrenalectomy on LH release in sheep during the anoestrous season

1987 ◽  
Vol 114 (3) ◽  
pp. 437-442 ◽  
Author(s):  
G. W. Montgomery ◽  
G. B. Martin ◽  
A. Locatelli ◽  
J. Pelletier
Keyword(s):  
Reproductive System ◽  
Seasonal Changes ◽  
Pulse Frequency ◽  
Adrenal Steroids ◽  
Unoperated Control ◽  
Future Studies ◽  
Lh Release ◽  
The Mean ◽  
Small Implants

ABSTRACT An experiment was conducted to measure LH pulse frequencies in bilaterally adrenalectomized Ile-de-France ewes during the mid-anoestrous season. Seven ewes were adrenalectomized under general anaesthesia and maintained on daily injections of 3 mg deoxycorticosterone acetate (DOCA). Adrenalectomy did not affect the patterns of LH release and the mean intervals between pulses in the adrenalectomized and sham-operated control ewes were 48 and 52 min respectively. Small implants of oestradiol significantly reduced the frequency of LH pulses in both groups and, in the presence of oestradiol, there were no differences in LH release between adrenalectomized and sham-operated ewes, with the mean interpulse intervals being 91 and 89 min respectively. In a second experiment, designed to assess the effects of DOCA on LH release, the mean interpulse intervals in unoperated control ewes (46 min) and unoperated ewes given daily injections of 3 mg DOCA (47 min) were similar to those observed in adrenalectomized and sham-operated ewes. In the presence of small implants of oestradiol, the combination of DOCA and oestradiol decreased the pulse frequency significantly more than oestradiol alone (mean interpulse intervals of 85 and 65 min respectively) suggesting that DOCA may act as a progestagen in sheep. Thus alternative treatments to DOCA for the maintenance of adrenalectomized sheep must be found for future studies on the role of adrenal steroids in the reproductive system. It appears that adrenal steroids do not play a major role in the seasonal changes in LH release in the ewe. J. Endocr. (1987) 114,437–442

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.

scholarly journals Two-week pulsatile gonadotropin releasing hormone infusion unmasks dual (hypothalamic and Leydig cell) defects in the healthy aging male gonadotropic axis

1999 ◽  
pp. 257-266 ◽  
Author(s):  
T Mulligan ◽  
A Iranmanesh ◽  
R Kerzner ◽  
LW Demers ◽  
JD Veldhuis
Keyword(s):  
Leydig Cell ◽  
Healthy Aging ◽  
Pulse Signal ◽  
Pulse Amplitude ◽  
Older Men ◽  
Pulse Frequency ◽  
Biologically Active ◽  
Cell Axis ◽  
Double Blind ◽  
Lh Release

OBJECTIVE: To examine the possibility that lower serum bioavailable testosterone concentrations, without increased LH release, in healthy older men, reflects hypothalamic GnRH deficiency. DESIGN: We used a randomized, double-blind, placebo-controlled design. METHODS: We treated each of five young (ages 20-34 years) and five older (ages 60-78 years) men with 2 weeks of randomized infusions of saline or pulsatile GnRH (100 ng/kg i.v. every 90 min). RESULTS: At baseline (saline infusion), older men had more LH pulses (young compared with old, 10 +/- 0.6 compared with 15 +/- 1, P = 0.0026) per 24h, reduced fractional LH pulse amplitude (219 +/- 17% compared with 167 +/- 40%, P = 0.0376), and more disorderly hormone release as judged by approximate entropy (ApEn) (LH, P < or = 0.0001; testosterone, P < or = 0.0047). In response to pulsatile i.v. GnRH infusions, serum 24-h LH concentrations (measured by immunoradiometric assay (IRMA)), increased equivalently in young and older men (to 7.3 +/- 1.2 and 7.2 +/- 1.8 IU/l respectively). GnRH treatment also normalized LH pulse frequency and amplitude, ApEn, and plasma biologically active LH (pooled) concentrations. In contrast, 24-h testosterone concentrations failed to increase equivalently in older men (young compared with old, 869 +/- 88 compared with 517 +/- 38 ng/dl, P = 0.0061), reflecting lower testosterone peak maxima (995 +/- 108 compared with 583 +/- 48 ng/dl, P = 0.0083) and interpeak nadirs (750 +/- 87 compared with 427 +/- 26 ng/dl, P = 0.0073). CONCLUSIONS: We have demonstrated that, in older men, successful reconstitution of 24-h pituitary (bioactive) LH output and pulsatile (IRMA) LH release patterns could be achieved by a fixed exogenous GnRH pulse signal, thereby implicating altered endogenous hypothalamic GnRH release in the relative hypogonadotropism of aging. The failure of testosterone concentrations to increase concomitantly points to a simultaneous Leydig cell defect. We conclude that aging in men is marked by a dual defect in the central nervous system-pituitary-Leydig cell axis.

Growth hormone pulsatility in ram lambs of genotypes selected for fatness or leanness

1993 ◽  
Vol 57 (1) ◽  
pp. 119-125 ◽  
Author(s):  
J. M. Suttie ◽  
B. A. Veenvliet ◽  
R. P. Littlejohn ◽  
P. D. Gluckman ◽  
I. D. Corson ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Sampling Period ◽  
Pulse Amplitude ◽  
Basic Mechanism ◽  
Pulse Frequency ◽  
Carcass Weight ◽  
Pulse Detection ◽  
Gh Secretion ◽  
Positive Effects

AbstractAlthough it is known that growth hormone (GH) influences body composition in ruminants, the precise role of the pattern of GH secretion is not known. We have studied the pulsatile release of GH and insulin-like growth factor 1 (IGF 1) secretion in the male progeny of rams from lines selected either for {fat genotype) or against (lean genotype) fatness. Seventy-two lambs (36 each of the fat and lean genotype) were kept on high-quality pasture and randomly allocated within genotype to treatment at 2, 3, 3·5, 4,5 or 6 months of age. The procedure, which was identical for each sampling period, was to sample each lamb through a jugular cannula every 10 min for 6 h, and then, following an overnight fast, to slaughter and analyse the carcass for fat. All blood samples were analysed for GH and samples taken each hour for total plasma IGF 1. The GH data were further analysed with the pulse detection routine PULSAR. Carcass fatness, adjusted for cold carcass weight, was greater for fat genotype animals than for the lean genotype. GH was pulsatile in all profiles but the pattern differed with time and genotype. Mean GH and pulse amplitude decreased with time but did not differ between genotype, although the lean genotype had higher mean GH at five of the six sampling periods. In contrast, GH pulse frequency and IGF 1 were significantly higher for the fat compared with the lean genotype lambs. GH mean and amplitude correlated negatively with carcass fatness in both genotypes and GH pulse frequency and total IGF 1 correlated positively with fatness for the lean genotype only. When carcass weight and genotype were fitted to these relationships, GH mean and total IGF 1 were found to have independent negative and positive effects, respectively, on carcass fatness. Because GH mean had a separate effect on fatness independent of genotype or cold carcass weight, it is likely that GH secretion influences composition by the same basic mechanism in both genotypes. However, although the slopes of these relationships did not differ significantly between the genotypes, the intercepts were significantly different indicating that over and above the basic mechanism, at any level of GH, the lean genotype lambs were leaner than the fat genotype lambs. This may indicate a measure ofGH resistance in the fat genotype lambs.

scholarly journals Reversal of the hypothalamo-pituitary–adrenal response to oestrogens around puberty

2009 ◽  
Vol 202 (2) ◽  
pp. 279-285 ◽  
Author(s):  
Obaro Evuarherhe ◽  
James Leggett ◽  
Eleanor Waite ◽  
Yvonne Kershaw ◽  
Stafford Lightman
Keyword(s):  
Corticosterone Level ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Female Rats ◽  
Inhibitory Effects ◽  
Sampling System ◽  
Gender Dimorphism ◽  
Adrenal Response ◽  
Hpa Axis Activity

The neuroendocrine gender dimorphism that begins during perinatal development is completed during puberty. We have previously described how the perinatal gonadal steroids programme hypothalamic–pituitary–adrenal (HPA) activity in adulthood and we now assess the role of peripubertal ovarian hormones. Prepubertal females were treated subcutaneously with either cholesterol or 17β-oestradiol and their pituitary–adrenal activity was assessed 5 days later. Oestradiol suppressed the ACTH and corticosterone responses to restraint stress in the prepubertal female. Furthermore, groups of female rats were ovariectomised (OVX) either before or after puberty and adult animals were subsequently treated with subcutaneous implants containing either 17β-oestradiol or cholesterol. Corticosterone pulsatility was assessed using an automated blood sampling system to collect blood from freely moving animals at 10 min intervals over 24 h. Oestradiol administered to adults that had been OVX either pre- or post-pubertally displayed a significantly higher mean corticosterone level as well as increased pulse frequency and pulse amplitude compared with cholesterol treated controls. These data demonstrate a reversal in the effect of oestrogens on HPA axis activity over the time of puberty with inhibitory effects prepubertally and stimulatory actions after puberty and imply an ovarian steroid-independent mechanism of pubertal maturation of HPA sensitivity to oestrogens.

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