Neuroendocrine Aspects of Female Reproductive Aging

Wise, Phyllis M.; Smith, Matthew J.

doi:10.1016/b978-012351830-9/50058-5

Cited by 1 publication

(2 citation statements)

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“…Our results clearly establish that cAMP rhythms exist in the SCN and rMPN, and that aging involves a waning of these cAMP rhythms in middle-aged rats. These brain regions work in concert to regulate the cyclic synthesis and secretion of GnRH and to induce reproductive behaviors (Wise and Smith, 2001). Our findings confirm and extend the previous study by Chappell et al (2000) who showed that cAMP levels display a diurnal rhythm in the AVPV.…”

Section: Discussionmentioning

confidence: 99%

“…The synchronization of these events is tightly coupled to environmental cues, such as the light/dark cycle, and circulating ovarian hormones, such as estradiol (Wise, 1999). As rats approach middle age, age-related deterioration in hypothalamic functions is a crucial element that contributes to reproductive decline (Wise et al, 1997Wise, 1999Wise, , 2000Wise and Smith, 2001). We found that the ability of the suprachiasmatic nucleus (SCN), the circadian pacemaker of the brain, to drive an array of diurnal neurochemical events diminishes with age, and this may explain the dampening and desynchronization of multiple neurotransmitter rhythms that lead to the age-related improper timing of GnRH-LH surges (Lloyd et al, 1994;Krajnak et al, 2001;Le et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Suppression of Vasoactive Intestinal Polypeptide in the Suprachiasmatic Nucleus Leads to Aging-Like Alterations in cAMP Rhythms and Activation of Gonadotropin-Releasing Hormone Neurons

Gerhold¹,

Rosewell²,

Wise³

2005

J. Neurosci.

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Input from the suprachiasmatic nucleus (SCN) to gonadotropin-releasing hormone (GnRH) neurons is critical to the occurrence of regular cyclic GnRH secretion. It is thought that an essential neuropeptide in the SCN that communicates this cyclic information to GnRH neurons is vasoactive intestinal polypeptide (VIP) and that it may act through cAMP. We tested the hypothesis that (1) aging involves a blunting of cAMP diurnal rhythmicity in the SCN; (2) administration of antisense oligonucleotides (anti-oligos) against VIP, which produces an aging-like pattern in VIP, would lead to an aging-like suppression of cAMP; and (3) this in turn would lead to inhibition of the steroid-induced activation of GnRH neurons. We measured cAMP concentrations in the SCN and rostral preoptic nucleus throughout the day in young and middle-aged rats that were ovariectomized (OVX) or OVX and treated with estradiol.Our results show that cAMP concentrations exhibit a diurnal rhythm in young rats, and that this rhythm is totally abolished by the time rats are middle age. Administration of antisense oligonucleotides against VIP or random oligos suppresses VIP concentrations and abolishes the cAMP rhythm, leading to significantly reduced activation of GnRH neurons. Together, these findings strongly suggest that the SCN conveys diurnal information to GnRH neurons by driving VIP-dependent cAMP rhythms. In addition, aging involves deterioration in this VIP-driven rhythmicity, which impacts the ability of steroids to induce GnRH neuronal activation.

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Section: Discussionmentioning

confidence: 99%