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Kisspeptins have emerged as potent elicitors of gonadotropin secretion and, therefore, putative targets for pharmacological intervention. In this context, desensitization of gonadotropin responses to continuous administration of kisspeptins has begun to be characterized, but information so far available is mostly restricted to LH responses in males, whereas the similar phenomenon in females, of obvious therapeutic interest, remains virtually unexplored. We report herein LH and FSH responses to continuous intracerebral administration of kisspeptin in female rats at different developmental and metabolic states. Infusion of kisspeptin-10 to adult female rats induced a transient elevation in serum LH concentrations, followed by a precipitous drop and normalization of LH levels thereafter. Elevation of LH after kisspeptin infusion was prolonged in underfed animals; a phenomenon mimicked by leptin administration. Conversely, FSH levels were persistently heightened along continuous kisspeptin infusion, but duration of this response was shortened by undernutrition. In pubertal females, LH and FSH levels remained elevated at the end of a 7-day infusion of kisspeptin; responses whose magnitude was augmented by subnutrition but not mimicked by leptin. In all settings, terminal gonadotropin-releasing hormone responses were fully preserved, suggesting that eventual desensitization must occur upstream from the pituitary. In summary, our current data document the pharmacological consequences of continuous administration of kisspeptin to female rats, with remarkable differences being detected between LH and FSH responses, in different developmental and metabolic states. These observations of potential pharmacological interest might help also to delineate the physiological roles of kisspeptins in the dynamic regulation of gonadotropin secretion in the female. [ABSTRACT FROM AUTHOR]

Reproductive function is exquisitely sensitive to adequacy of nutrition and fuel reserves, through mechanisms that are yet to be completely elucidated. Galanin-like peptide (GALP) has recently emerged as another neuropeptide link that couples reproduction and metabolism. However, although the effects of GALP on luteinizing hormone (LH) secretion have been studied, no systematic investigation on how these responses might differ along sexual maturation and between sexes has been reported. Moreover, the influence of metabolic status and potential interplay with other relevant neurotransmitters controlling LH secretion remain ill defined. These facets of GALP physiology were addressed herein. Intracerebral injection of GALP to mate rats induced a dose-dependent increase in serum LH levels, the magnitude of which was significantly greater in pubertal than in adult mates. In contrast, negligible LH responses to GALP were detected in pubertal or adult female rats at diestrus. Neonatal androgen treatment to females failed to "masculinize" the pattern of LH response to GALP. In addition, metabolic stress by short-term fasting did not prevent but rather amplified LH responses to GALP in pubertal males, whereas these responses were abrogated by pharmacological inhibition of nitric oxide synthesis. We conclude that the ability of GALP to evoke LH secretion is sexually differentiated, with maximal responses at male puberty, a phenomenon which was not reverted by manipulation of sex steroid milieu during the critical neonatal period and was sensitive to metabolic stress. This state of LH hyperresponsiveness may prove relevant for the mechanisms relaying metabolic status to the reproductive axis in male puberty. [ABSTRACT FROM AUTHOR]

Development and normal function of the reproductive axis requires a precise degree of body energy stores. Polypeptide YY-(3-36) [PYY-(3-36)] is a gastrointestinal secreted molecule recently shown to be involved in the control of food intake with agonistic activity on neuropeptide Y (NPY) receptor subtypes Y2 and Y5. Notably, PYY-(3-36) has been recently demonstrated as putative regulator of gonadotropin secretion in the rat. However, the ‘reproductive’ facet of this factor remains to be fully elucidated. In this context, we report herein our analyses of the influence of the nutritional status on the effects of PYY-(3-36) upon GnRH and gonadotropin secretion. The major findings of our study are 1) the stimulatory effect of central administration of PYY-(3-36) on LH secretion was significantly enhanced after fasting and blocked by a GnRH antagonist; 2) besides central effects, PYY-(3-36) elicited LH and FSH secretion directly at the pituitary level, a response that is also augmented by fasting; 3) PYY-(3-36) inhibited GnRH secretion by hypothalamic fragments from male rats fed ad libitum, whereas a significant stimulatory effect was observed after fasting; and 4) the increase in the gonadotropin responsiveness to PYY-(3-36) in fasting was not associated with changes in the expression of Y2 and Y5 receptor genes at hypothalamus and/or pituitary. In conclusion, our study extends our previous observations suggesting a relevant, mostly stimulatory, role of PYY-(3-36) in the control of gonadotropin secretion. Strikingly, such an effect was significantly enhanced by fasting. Considering the proposed decrease in PYY-(3-36) levels after fasting, the possibility that reduced PYY-(3-36) secretion might contribute to defective function of the gonadotropic axis after food deprivation merits further investigation. [ABSTRACT FROM AUTHOR]

The close link between reproductive function and body energy stores relies on a complex neuroendocrine network of common regulatory signals, the nature of which is yet to be fully elucidated. Recently, 26RFa was identified in amphibians and mammals as a conserved hypothalamic neuropeptide of the RFamide family, with a potent orexigenic activity. Yet, despite its proposed role as hypophysiotropic factor, the function of 26RFa in the control of pituitary gonadotropins and, hence, of the reproductive axis remains unexplored. In the present study, the effects of 26RFa on gonadotropin secretion were evaluated in the rat by a combination of in vitro and in vivo approaches. At the pituitary, 26RFa dose-dependently enhanced basal and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone (LH) secretion from male and cyclic female rats. This effect was mimicked by the active fragment 26RFa20–26, as well as by the related 43RFa peptide. Moreover, expression of the genes encoding 26RFa and its putative receptor, GPR103, was demonstrated in rat pituitary throughout postnatal development. In vivo, intracerebral injection of 26RFa evoked a significant increase in serum LH levels in cyclic and ovariectomized females; this response which was also observed after central injection of 26RFa20–26 and 43RFa peptides, as well as after systemic administration of 26RFa. Conversely, central and systemic injection of 26RFa failed to significantly modify gonadotropin secretion in adult male rats, even after repeated administration of the peptide. In summary, we present herein novel evidence for the potential role of the orexigenic peptide 26RFa in the control of the gonadotropic axis, thus suggesting its potential involvement in the joint control of energy balance and reproduction, especially in the female. [ABSTRACT FROM AUTHOR]

Iberian pig is the most abundant Mediterranean swine. The lack of knowledge of the reproductive physiology of Mediterranean genotypes, with predisposition to obesity, led us to evaluate the influence of body condition and metabolic status at weaning on the resumption of follicular growth and the appearance of post-weaning oestrus. Females failing to display post-weaning oestrus showed a high decrease in backfat mass during lactation; backfat depth at weaning was therefore lower than in sows becoming in oestrus. Females not bearing oestrus behaviour showed lower plasma leptin levels and higher ghrelin concentrations at weaning. Moreover, these sows evidenced dyslipidemic profile (increased triglyceridemia and cholesterolemia) and mobilization of fat reserves. Hence, changes in metabolic regulation of Iberian pigs may originate large effects on the resumption of ovulatory activity after weaning. [ABSTRACT FROM AUTHOR]