scholarly journals A potential apulsatile mode of GnRH release in the male rhesus monkey (Macaca mulatta)

1999 ◽  
Vol 163 (2) ◽  
pp. 235-241 ◽  
Author(s):  
KJ Suter
Keyword(s):  
Macaca Mulatta ◽  
Gnrh Antagonist ◽  
Pulse Generator ◽  
Physiological Saline ◽  
Similar Reduction ◽  
Gnrh Release ◽  
Lh Release ◽  
Lh Secretion ◽  
Circulating Levels ◽  
Male Rhesus

The hypothalamic component of the reproductive axis in vertebrates is comprised of a pulse generator that stimulates the release of GnRH. Several lines of evidence are in agreement that the activity of this pulse generator is intermittent and results in the pulsatile pattern of GnRH and LH release. During a recent investigation of the re-initiation of LH secretion in the agonadal, prepubertal male monkey, we observed a daytime profile of LH secretion, which suggests an apulsatile mode of GnRH release. The first purpose of this study was to describe this observation of apulsatile LH release during the peripubertal transition. Furthermore, we have explored the dependence of this form of LH secretion on GnRH release. Five male rhesus monkeys (Macaca mulatta) were castrated prepubertally and were treated with an intermittent infusion of GnRH to prematurely sensitize the juvenile pituitary to endogenous GnRH release. Alternate daytime (1100-1800 h) and nighttime (1900-0200 h) assessments of LH release were performed at 10-day intervals throughout the peripubertal transition with samples taken every 12 min. In a second experiment, four agonadal males which demonstrated an apulsatile profile of LH release were maintained on an infusion of physiological saline and were treated with the GnRH antagonist Nal-Glu (i.m., 500 microgram/kg). Circulating levels of LH were determined 22 h after antagonist treatment. In peripubertal animals, circulating levels of LH were similar between morning and evening assessments. However, pulse frequency was significantly lower during the daytime. GnRH antagonist reduced LH levels by 72% and a similar reduction in response to an exogenous GnRH test stimulus occurred. These findings suggest an apulsatile mode of GnRH release.

Androgenic and oestrogenic steroid participation in feedback control of luteinizing hormone secretion in male sheep

1983 ◽  
Vol 102 (4) ◽  
pp. 499-504 ◽  
Author(s):  
M. J. D'Occhio ◽  
B. D. Schanbacher ◽  
J. E. Kinder
Keyword(s):  
Luteinizing Hormone ◽  
Pulse Generator ◽  
Hormone Secretion ◽  
Pulse Interval ◽  
Serum Concentrations ◽  
Luteinizing Hormone Secretion ◽  
Lh Release ◽  
Lh Secretion ◽  
Additional Feedback ◽  
Male Sheep

Abstract. The acute castrate ram (wether) was used as an experimental model to investigate the site(s) of feedback on luteinizing hormone (LH) by testosterone, dihydrotestosterone and oestradiol. At the time of castration, wethers were implanted subdermally with Silastic capsules containing either crystalline testosterone (three 30 cm capsules), dihydrotestosterone (five 30 cm capsules) or oestradiol (one 6.5 cm capsule). Blood samples were taken at 10 min intervals for 6 h 2 weeks after implantation to determine serum steroid concentrations and to characterize the patterns of LH secretion. Pituitary LH response to exogenous LRH (5 ng/kg body weight) were also determined at the same time. The steroid implants produced serum concentrations of the respective hormones which were either one-third (testosterone) or two-to-four times (dihydrotestosterone, oestradiol) the levels measured in rams at the time of castration. Non-implanted wethers showed rhythmic pulses of LH (pulse interval 40–60 min) and had elevated LH levels (16.1 ± 1.6 ng/ml; mean ± se) 2 weeks after castration. All three steroids suppressed pulsatile LH release and reduced mean LH levels (to below 3 ng/ml) and pituitary LH responses to LRH. Inhibition of pulsatile LH secretion by all three steroids indicated that testosterone as well as its androgenic and oestrogenic metabolites can inhibit the LRH pulse generator in the hypothalamus. Additional feedback on the pituitary was indicated by the dampened LH responses to exogenous LRH.

scholarly journals Characterization of the Role of NKA in the Control of Puberty Onset and Gonadotropin Release in the Female Mouse

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2453-2463 ◽  
Author(s):  
Silvia León ◽  
Chrysanthi Fergani ◽  
Rajae Talbi ◽  
Serap Simavli ◽  
Caroline A Maguire ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Neurokinin A ◽  
Central Control ◽  
Gnrh Release ◽  
Lh Release ◽  
Timing Of Puberty ◽  
Puberty Onset ◽  
Lh Secretion

Abstract The tachykinin neurokinin B (NKB, Tac2) is critical for proper GnRH release in mammals, however, the role of the other tachykinins, such as substance P (SP) and neurokinin A (NKA) in reproduction, is still not well understood. In this study, we demonstrate that NKA controls the timing of puberty onset (similar to NKB and SP) and stimulates LH release in adulthood through NKB-independent (but kisspeptin-dependent) mechanisms in the presence of sex steroids. Furthermore, this is achieved, at least in part, through the autosynaptic activation of Tac1 neurons, which express NK2R (Tacr2), the receptor for NKA. Conversely, in the absence of sex steroids, as observed in ovariectomy, NKA inhibits LH through a mechanism that requires the presence of functional receptors for NKB and dynorphin (NK3R and KOR, respectively). Moreover, the ability of NKA to modulate LH secretion is absent in Kiss1KO mice, suggesting that its action occurs upstream of Kiss1 neurons. Overall, we demonstrate that NKA signaling is a critical component in the central control of reproduction, by contributing to the indirect regulation of kisspeptin release.

scholarly journals Repetitive Activation of Hypothalamic G Protein-Coupled Receptor 54 with Intravenous Pulses of Kisspeptin in the Juvenile Monkey (Macaca mulatta) Elicits a Sustained Train of Gonadotropin-Releasing Hormone Discharges

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 1007-1013 ◽  
Author(s):  
Tony M. Plant ◽  
Suresh Ramaswamy ◽  
Meloni J. DiPietro
Keyword(s):  
G Protein ◽  
Concomitant Treatment ◽  
Secondary Effects ◽  
G Protein Coupled Receptor ◽  
Gnrh Release ◽  
Dependent Signal ◽  
Lh Release ◽  
Lh Secretion ◽  
G Protein Coupled

The purpose of the present study was to further examine the hypothesis that activation of G protein-coupled receptor 54 (GPR54) signaling at the end of the juvenile phase of primate development is responsible for initiation of gonadarche and the onset of puberty. Accordingly, we determined whether repetitive iv administration of the GPR54 receptor agonist kisspeptin-10 (2 μg as a brief 1-min infusion once every hour for 48 h) to the juvenile male rhesus monkey would prematurely elicit sustained, pulsatile release of hypothalamic GnRH, the neuroendocrine trigger for gonadarche. GnRH release was monitored indirectly by measuring LH secretion from the in situ pituitary, the GnRH responsiveness of which had been heightened before the experiment with an intermittent iv infusion of synthetic GnRH. Agonadal animals (n = 4) were employed to eliminate any confounding and secondary effects of changing feedback signals from the testis. The first brief infusion of kisspeptin-10 evoked an LH discharge that mimicked those produced by GnRH priming, and this was followed by a train of similar LH discharges in response to hourly activation of GPR54 by repetitive kisspeptin-10 administration. Concomitant treatment with a GnRH receptor antagonist, acyline, abolished kisspeptin-10-induced LH release. Repetitive kisspeptin-10 administration also provided a GnRH-dependent signal to FSH secretion. These findings are consistent with the notion that, in primates, the transition from the juvenile (attenuated GnRH release) to pubertal (robust GnRH release) state is controlled by activation of GPR54 resulting from increased expression of hypothalamic KiSS-1 and release of kisspeptin in this region of the brain.

scholarly journals The Gonadotropin-Releasing Hormone Pulse Generator

Endocrinology ◽  
2018 ◽  
Vol 159 (11) ◽  
pp. 3723-3736 ◽  
Author(s):  
Allan E Herbison
Keyword(s):  
Arcuate Nucleus ◽  
Pulse Generator ◽  
Pulse Generation ◽  
Sufficient Evidence ◽  
Gnrh Neuron ◽  
Lh Pulsatility ◽  
Intrinsic Mechanism ◽  
Lh Release ◽  
Lh Secretion ◽  
Present Understanding

Abstract The pulsatile release of GnRH and LH secretion is essential for fertility in all mammals. Pulses of LH occur approximately every hour in follicular-phase females and every 2 to 3 hours in luteal-phase females and males. Many studies over the last 50 years have sought to identify the nature and mechanism of the “GnRH pulse generator” responsible for pulsatile LH release. This review examines the characteristics of pulsatile hormone release and summarizes investigations that have led to our present understanding of the GnRH pulse generator. There is presently little compelling evidence for an intrinsic mechanism of pulse generation involving interactions between GnRH neuron cell bodies. Rather, data support the presence of an extrinsic pulse generator located within the arcuate nucleus, and attention has focused on the kisspeptin neurons and their projections to GnRH neuron dendrons concentrated around the median eminence. Sufficient evidence has been gathered in rodents to conclude that a subpopulation of arcuate kisspeptin neurons is, indeed, the GnRH pulse generator. Findings in other species are generally compatible with this view and suggest that arcuate/infundibular kisspeptin neurons represent the mammalian GnRH pulse generator. With hindsight, it is likely that past arcuate nucleus multiunit activity recordings have been from kisspeptin neurons. Despite advances in identifying the cells forming the pulse generator, almost nothing is known about their mechanisms of synchronicity and the afferent hormonal and transmitter modulation required to establish the normal patterns of LH pulsatility in mammals.

scholarly journals Inhibition of Gonadotropin-Induced Testosterone Secretion by the Intracerebroventricular Injection of Interleukin-1β in the Male Rat*

Endocrinology ◽  
1997 ◽  
Vol 138 (3) ◽  
pp. 1008-1013 ◽  
Author(s):  
Andrew V. Turnbull ◽  
Catherine Rivier
Keyword(s):  
Gnrh Antagonist ◽  
Plasma Corticosterone ◽  
Male Rat ◽  
Neural Pathways ◽  
Central Administration ◽  
Testosterone Secretion ◽  
Central Origin ◽  
Lh Secretion ◽  
The Brain ◽  
Circulating Levels

Abstract The intracerebroventricular (icv) injection of the proinflammatory cytokine interleukin (IL)-1β is known to significantly decrease plasma LH levels in the male rat, thereby lowering testosterone (T) secretion. We show here that central administration of this cytokine (20–80 ng) also inhibits T secretion in response to human CG (hCG), an effect that is apparent already when IL-1β is injected 15 min before hCG. This phenomenon is independent of LH secretion because lowering LH levels with the potent GnRH antagonist Azaline B neither mimics nor affects the suppressive influence of icv IL-1β on the hCG-induced T secretory response. Elevations in plasma corticosterone levels do not seem to play a role either, because icv IL-1β is able to blunt hCG-induced T secretion in animals whose corticosterone has been removed by adrenalectomy or reduced by the administration of antibodies to CRF. Furthermore, the observation that icv IL-1β inhibits the T response to hCG before elevations in plasma IL-6 concentrations are detectable, and that central treatment with the cytokine is more effective than iv treatment, indicates that circulating levels of neither IL-1β nor IL-6 are important mediators of this effect. Collectively, these results lead us to propose that IL-1β of central origin influences neural pathways linking the brain and the testes, resulting in decreased testicular responses to hCG.

scholarly journals Indirect assessment of pulsatile gonadotropin-releasing hormone release in agonadal prepubertal rhesus monkeys (Macaca mulatta)

1999 ◽  
Vol 160 (1) ◽  
pp. 35-41 ◽  
Author(s):  
KJ Suter ◽  
CR Pohl ◽  
TM Plant
Keyword(s):  
Pulse Generator ◽  
Intermittent Infusion ◽  
Open Loop ◽  
Remote Access ◽  
Striking Difference ◽  
Major Purpose ◽  
Venous Circulation ◽  
Pulsatile Gnrh ◽  
Gnrh Release ◽  
Lh Secretion

The major purpose of this study was to characterize the open-loop frequency of pulsatile GnRH release in the female rhesus monkey at an age (15-20 months) when the prepubertal restraint on the hypothalamic-pituitary axis is maximally imposed. Additionally, evidence for pulsatile GnRH release in agonadal males of comparable age was also sought. Episodic LH secretion from the pituitary was used as an indirect index of GnRH discharges. In order to maximize the sensitivity of this in situ bioassay, the responsiveness of the pituitary gonadotrophs was usually first heightened by an i.v. intermittent infusion of the synthetic peptide. Monkeys (five females, three males) were castrated between 9 and 14 months of age, implanted with indwelling venous catheters, fitted with nylon jackets and housed in specialized cages that permitted remote access to the venous circulation with minimal restraint and without interruption of the light-darkness cycle. In females, LH secretion was generally assessed at 20-day intervals during alternate nighttime (1900-0200 h) and daytime (0700-1400 h) windows. In males, LH was assessed less frequently and only at night. The mean frequency of pulsatile LH release in agonadal prepubertal females was 4 pulses/7 h during the night and 2 pulses/7 h during the day. These findings indicate that, prior to puberty in the female monkey, the GnRH pulse generator operates at a relatively slow frequency and is subjected to diurnal modulation. In males, evidence for robust pulsatile GnRH release was not observed. The striking difference in activity of the GnRH pulse generator in agonadal prepubertal male and female monkeys reinforces the view that the ontogeny of the hypothalamic drive to the pituitary-gonadal axis in higher primates, including man, is sexually differentiated.

Attempts to activate a pubertal pattern of GnRH release in juvenile male rhesus monkeys (Macaca mulatta) with continuous low dose infusions of human metastin 45–54

2006 ◽  
Vol 27 (1) ◽  
pp. 140
Author(s):  
Meloni J. DiPietro ◽  
Suresh Ramaswamy ◽  
Stephanie B. Seminara ◽  
William F. Crowley Jr. ◽  
Tony M. Plant
Keyword(s):  
Macaca Mulatta ◽  
Rhesus Monkeys ◽  
Low Dose ◽  
Juvenile Male ◽  
Gnrh Release ◽  
Male Rhesus

Effect of GnRH and its antagonist (Antarelix) on LH release from cultured bovine anterior pituitary cells

2002 ◽  
Vol 50 (1) ◽  
pp. 79-92 ◽  
Author(s):  
Annett Bellmann ◽  
F. Schneider ◽  
W. Kanitz ◽  
Keyword(s):  
Anterior Pituitary ◽  
Culture System ◽  
Gnrh Antagonist ◽  
Pituitary Cells ◽  
Maximal Effect ◽  
Static Culture ◽  
Lh Release ◽  
Lh Secretion

In the following investigations, the LH secretion of cells from pituitaries in heifers on days 16-18 of their oestrous cycle (n = 14) was analysed. Cells were dissociated with trypsin and collagenase and maintained in a static culture system. For the estimation of LH release, the cells were incubated with various concentrations of mammalian GnRH (Lutrelef) for 6h. To determine the action of Antarelix (GnRH antagonist), the cells were preincubated for 1 h with concentrations of 10-5 or 10-4 M Antarelix followed by 10-6 M GnRH coincubation for a further 6h. At the end of each incubation, the medium was collected for LH analysis. Parallel, intracellular LH was qualitatively detected by immunocytochemistry. Changes in the intensity of LH staining within the cells in dependence of different GnRH concentrations were not observed, but a significant increase LH secretion in pituitary cells was measured at 10-6 M GnRH. Antarelix had no effect on basal LH secretion at concentrations of 10-4 and 10-5 M. After coincubation of pituitary cells with Antarelix and GnRH, Antarelix blocked the GnRH-stimulated LH secretion with a maximal effect of 10-4 M, but the staining of immunoreactive intracellular LH was detected at approximately the same level compared to the pituitary cells treated with exogenous GnRH alone. These data demonstrate that Antarelix is effective in influencing the GnRH-stimulated LH secretion of pituitary cells in vitro. After administration of Antarelix in vivo, the GnRH-stimulated LH secretion of cultured pituitary cells was not inhibited.

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