Fasting Reduces KiSS‐1 Expression in the Anteroventral Periventricular Nucleus (AVPV): Effects of Fasting on the Expression of KiSS‐1 and Neuropeptide Y in the AVPV or Arcuate Nucleus of Female Rats

Abstract

Changes in metabolic state, such as those induced by fasting, have profound effects on reproduction. In rats, the time-course over which fasting inhibits luteinising hormone (LH) release is reduced to 48 h by the presence of oestradiol-17beta (E(2)). Hypothalamic kisspeptin plays a key role in mediating the actions of E(2) on gonadotrophin-releasing hormone (GnRH) neurones, and thereby promotes LH release. KiSS-1-expressing neurones are found in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). Extensive evidence implicates the AVPV in GnRH release and the ARC in energy balance. The latter nucleus also contains neurones that express neuropeptide Y (NPY), an orexigenic peptide implicated in GnRH control. To elucidate the involvement of kisspeptin and/or NPY in hypothalamic responses to fasting, their expression was quantified by in situ hybridisation histochemistry in ovariectomised rats, with or without E(2) replacement, before and after 48 h of fasting. In the presence of E(2), but not in its absence, the fasting suppressed plasma LH. In the AVPV, the low level of KiSS-1 expression found in the absence of E(2) was unaffected by fasting. By contrast, the elevated level found in the presence of E(2) was suppressed by fasting. Independent of E(2), fasting had no effect on KiSS-1 expression in the ARC, but increased NPY expression at that site. The present study has identified the AVPV as a site at which KiSS-1 expression can be influenced by fasting. The results suggest that inhibition of KiSS-1 expression in the AVPV may be a significant factor in restraining the gonadotrophic axis in response to negative energy balance in the presence of oestrogen. The extent to which the concurrent rise in NPY expression in the ARC may contribute to the suppression of LH release by influencing AVPV kisspeptin neurones, directly or indirectly, or by actions independent of kisspeptin, remains to be established.

ENDOCRINOLOGY AND ADOLESCENCE: Deciphering puberty: novel partners, novel mechanisms

“…Conversely, administration of kisspeptin is sufficient to partially reverse the state of hypogonadotropism and delayed puberty caused by chronic under-nutrition in prepubertal female rats (55). Similar observations have been made in adult models of metabolic stress (57,58,59,60), where the hypothalamic Kiss1 tone is supposedly inhibited and the hypogonadotropic state rescued by exogenous kisspeptin. In this context, recognition of the expression of the mRNA encoding the functional leptin receptor, LepRb o Ob-Rb, in ARC Kiss1 neurons in the mouse and sheep (59,61), and the demonstration of the ability of leptin, at high doses, to increase the hypothalamic expression of Kiss1 gene in different models of severe metabolic stress, such as the leptin-deficient ob/ob mouse and the diabetic rat, fueled the hypothesis that leptin acts directly on Kiss1 neurons to conduct its stimulatory/permissive effects on GnRH neurons (57,58,59).…”

Metabolic control of puberty onset: New players, new mechanisms

“…While the precise location for such changes awaits further clarification, studies in female rats subjected to chronic calorie restriction along puberty (20% for 7 days) demonstrated a detectable suppression of Kiss1 expression at the arcuate nucleus (ARC) [39], where a prominent population of kisspeptin neurons resides [37]. Notwithstanding, additional changes in Kiss1 expression at the anteroventral periventricular nucleus (AVPV) cannot be excluded in pubertal females under more extreme conditions of food deprivation, in keeping with analogous observations in adult female rats subjected to 48-h fasting [40]. From a functional standpoint, such a decrease in Kiss1 expression seems causative for the perturbation (delay) in the timing of puberty at conditions of persistent energy balance, as suggested by our studies in a model of chronic subnutrition during the pubertal transition in female rats, as pharmacological 'replacement' with kisspeptin at the expected time of puberty in this model, without any other metabolic intervention, was sufficient to rescue vaginal opening (in a subset of animals) and to induce potent gonadotropic and estrogenic responses, despite the prevailing suppression of circulating levels of gonadotropins due to chronic subnutrition [38].…”

Kisspeptin and energy balance in reproduction

“…In a different altered energy state, an induced diabetic rat model, there was a significant decrease in Kiss1 mRNA compared with controls (Castellano et al 2006). In follow-up studies isolating the distinct populations of Kiss1, fasting reduced expression in the AVPV, but not the ARC, in adult female ovariectomized (OVX) rats (Kalamatianos et al 2008). Alternatively, chronic calorie restriction in female rats at the age of puberty reduced Kiss1 expression in the ARC, but not the AVPV ).…”