Astressin B, a Nonselective Corticotropin-Releasing Hormone Receptor Antagonist, Prevents the Inhibitory Effect of Ghrelin on Luteinizing Hormone Pulse Frequency in the Ovariectomized Rhesus Monkey

Vulliemoz, Nicolas; Xiao, Ennian; Xia‐Zhang, Linna; Rivier, Jean; Ferin, Michel

doi:10.1210/en.2007-1350

Cited by 63 publications

(41 citation statements)

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“…Stress has been linked to infertility in adult men (29), lower sperm motility in medical students (30), reduced proceptive sexual behavior (5), and fewer successful impregnations (8) by male rats, as well as lower hatchling survival in free-living European starlings (31). In addition, the effects of malnutrition on reproduction may result from activation of the stress system (32,33), suggesting that the importance of stress effects on the HPG may extend beyond traditional stressors. The HPA axis has also been implicated in aging and the increase in reproductive dysfunction with age (34).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, given the common interaction of HPA and HPG axes across many species and the similarity of GnIH/RFRP actions in birds and mammals (48), the involvement of RFRP in the HPA-HPG interaction investigated here in rats is predicted to be pertinent to most vertebrates. HPA axis activation is implicated in a number of causes of infertility and reproductive dysfunction, including chronic stress and malnutrition (32,33,49), and may significantly influence the efficacy of assisted reproductive procedures in humans (36,50). In addition, chronic stress is of primary concern in captive breeding programs as well as in agricultural breeding programs (51).…”

Section: Discussionmentioning

confidence: 99%

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Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats

Kirby

Geraghty

Ubuka

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

324

228

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The subjective experience of stress leads to reproductive dysfunction in many species, including rodents and humans. Stress effects on reproduction result from multilevel interactions between the hormonal stress response system, i.e., the hypothalamic-pituitary-adrenal (HPA) axis, and the hormonal reproductive system, i.e., the hypothalamic-pituitary-gonadal (HPG) axis. A novel negative regulator of the HPG axis known as gonadotropin-inhibitory hormone (GnIH) was recently discovered in quail, and orthologous neuropeptides known as RFamide-related peptides (RFRPs) have also been identified in rodents and primates. It is currently unknown, however, whether GnIH/RFRPs influence HPG axis activity in response to stress. We show here that both acute and chronic immobilization stress lead to an up-regulation of RFRP expression in the dorsomedial hypothalamus (DMH) of adult male rats and that this increase in RFRP is associated with inhibition of downstream HPG activity. We also show that adrenalectomy blocks the stress-induced increase in RFRP expression. Immunohistochemistry revealed that 53% of RFRP cells express receptors for glucocorticoids (GCs), indicating that adrenal GCs can mediate the stress effect through direct action on RFRP cells. It is thought that stress effects on central control of reproduction are largely mediated by direct or indirect effects on GnRH-secreting neurons. Our data show that stress-induced increases in adrenal GCs cause an increase in RFRP that contributes to hypothalamic suppression of reproductive function. This novel insight into HPA-HPG interaction provides a paradigm shift for work on stress-related reproductive dysfunction and infertility, and indicates that future work on stress and reproductive system interactions must include investigation of the role of GnIH/RFRP.GnIH ͉ reproduction ͉ RFRP S tress has acute and chronic effects on many aspects of vertebrate physiology and behavior. Reproduction is a key life-history component that is often adversely affected by physical and psychological stressors. The negative impact of stress occurs at several levels of the vertebrate hypothalamic-pituitary-gonadal (HPG) axis. Centrally, it leads to activation of the hypothalamic-pituitaryadrenal (HPA) axis, which in turn leads to suppression of HPG activity through inhibition of gonadotropin-releasing hormone (GnRH) secretion (1, 2). Downstream of GnRH, the functional effects of stress on reproduction can be seen with suppression of luteinizing hormone (LH) release from the pituitary (3, 4) and suppression of sexual behavior (5, 6). The stress effect on HPG function appears to be mediated by the adrenal stress hormones glucocorticoids (GCs). In male mammals, systemic GC administration inhibits circulating gonadotropin levels (7), decreases seminal vesicle weight, and results in fewer implantation sites and viable fetuses in female mates (8). However, hypothalamic corticotropinreleasing hormone (CRH) has also been strongly implicated in stress effects on reproduction (2, 9, 10).Gonadotropin i...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats

Kirby

Geraghty

Ubuka

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

324

228

View full text Add to dashboard Cite

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“…Circumstantial evidence, however, suggests an indirect mode of action, as ghrelin effects on LH secretion were inhibited by a non-selective antagonist of corticotrophin-releasing hormone (CRH) [34], and ghrelin was able to inhibit the effect of central elicitors of GnRH/gonadotropin release, such as kisspeptin [29]. In this sense, very recent evidence suggests that ghrelin is able to suppress Kiss1 gene expression at discrete hypothalamic areas [35], thus providing the neuroendocrine basis for, at least part of, its inhibitory effects on puberty onset and gonadotropin secretion.…”

Section: Ghrelin and Puberty Onset: Modulatory Actions In The Male Anmentioning

confidence: 99%

Metabolic control of puberty onset: New players, new mechanisms

Roa

García-Galiano

Castellano

et al. 2010

Molecular and Cellular Endocrinology

165

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Puberty, as the end-point of a complex series of maturational events affecting the components of the hypothalamic-pituitary-gonadal (HPG) axis, is gated by the state of body energy reserves and sensitive to different metabolic cues; conditions of severe metabolic stress and energy unbalance (from anorexia to morbid obesity) being commonly linked to perturbation of the onset of puberty. In the last two decades, the neuroendocrine mechanisms responsible for the tight coupling between energy homeostasis and puberty onset have begun to be deciphered. These seemingly involve a plethora of metabolic hormones and neuropeptides, which impinge and integrate (mostly) at the hypothalamic centers governing reproduction. Yet, characterization of the mechanisms of action of such regulators (and even their nature and physiological relevance) still remains incomplete. In this review, we will summarize some recent developments in our knowledge of the effects and mechanisms of action of two key metabolic hormones, leptin and ghrelin, in the control of puberty onset. In addition, the roles of the hypothalamic Kiss1 system in the metabolic gating of puberty will be reviewed, with special attention to its regulation by leptin and the recent identification of the putative roles of Crtc1 and mTOR signaling as molecular conduits for the metabolic control of Kiss1 expression. Elucidation of these novel players and regulatory mechanisms will help for a better understanding of the determinants of the timing of puberty, and its eventual alterations in adverse metabolic conditions.

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“…Vulliémoz et al [34] have recently indicated that corticotrophin-releasing hormone (CRH) may be involved in the inhibitory actions of ghrelin on LH secretion in rhesus monkey. Moreover, orexin reportedly mediated ghrelin-induced food intake in the rat [6], and we have also clarified that orexin A suppresses LH secretion not only via β-END but also via CRH and urocortin 2 [35].…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic Ghrelin Suppresses Pulsatile Secretion of Luteinizing Hormone via β-Endorphin in Ovariectomized Rats

et al. 2009

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Objectives: Ghrelin, an endogenous growth hormone secretagogue, is a known accelerator of feeding behavior and suppresses pulsatile secretion of luteinizing hormone (LH) in ovariectomized rats. However, the mechanisms underlying this action remain unclear. We examined the effects of naloxone (NAL), a specific opioid antagonist, on the suppression of pulsatile LH secretion by ghrelin to determine whether β-endorphin (β-END) is involved in this suppressive effect. Methods: Ghrelin was administered intracerebroventricularly, and NAL was injected intravenously in ovariectomized rats; then, serum LH concentrations were measured by radioimmunoassay in blood samples drawn every 6 min for 2 h to analyze pulsatile secretion. Results: Administration of ghrelin significantly reduced mean LH concentration and pulse frequency. Coadministration of NAL with ghrelin significantly restored mean LH concentration and pulse frequency. Conclusion: Suppressive effect of intracerebroventricular injection of ghrelin on pulsatile LH secretion was mediated by β-END, suggesting that hypothalamic ghrelin suppressed pulsatile gonadotropin-releasing hormone secretion via β-END in female rats.

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Astressin B, a Nonselective Corticotropin-Releasing Hormone Receptor Antagonist, Prevents the Inhibitory Effect of Ghrelin on Luteinizing Hormone Pulse Frequency in the Ovariectomized Rhesus Monkey

Cited by 63 publications

References 60 publications

Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats

Stress increases putative gonadotropin inhibitory hormone and decreases luteinizing hormone in male rats

Metabolic control of puberty onset: New players, new mechanisms

Hypothalamic Ghrelin Suppresses Pulsatile Secretion of Luteinizing Hormone via β-Endorphin in Ovariectomized Rats

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