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RF-amide related peptides (RFRP), as putative mammalian orthologs of the avian gonadotropin-inhibitory hormone (GnIH), have been proposed as key regulators of gonadotropin secretion in higher vertebrates. Yet considerable debate has arisen recently on their physiological relevance and potential mechanisms and sites of action. Present studies were undertaken to further characterize the effects of RFRP on LH and FSH secretion by a combination of in vivo and in vitro approaches in male and female rats. Initial screening via intracerebroventricular (icy) administration of different analogs of RFRP1 (RFRP1-12 and RFRP1--20) and RFRP3 (RFRP3--8 and RFRP3--17), as well as the related neuropeptide FF (NPFF8), to gonadectomized (GNX) female rats evidenced significant, albeit modest, inhibitory effects on LH secretion only for RFRP3--8 and RFRP3--17, which were detectable at the high dose rage (1 nmol for RFRP3--8, 5 nmol for RFRP3--17). This moderate inhibitory action was also documented after icv administration of RFRP3--8 to intact and GNX male rats. In addition, systemic (intravenous) administration of RFRP3--8 decreased the circulating levels of both gonadotropins in GNX male rats. Likewise, RFRP3--8 inhibited basal and GnRH-stimulated LH secretion by pituitaries from GNX males in vitro. This inhibitory effect was blocked by the antagonist of RFRP receptors, RF9. In summary, our results support a putative inhibitory role of RFRP3 as ortholog of GnIH in the regulation of gonadotropin secretion in mammals, which appears to involve direct pituitary actions as well as potential central (hypothalamic) effects. RF-amide related peptide; gonadotropin-inhibitory hormone; gonadotropin-releasing hormone; neuropeptide FF; receptor; RF9 doi: 10.1152/ajpendo.00108.2010.

Severe inflammatory challenges are frequently coupled to decreased food intake and disruption of reproductive function, the latter via deregulation of different signaling pathways that impinge onto GnRH neurons. Recently, the hypothalamic Kiss1 system, a major gatekeeper of GnRH function, was suggested as potential target for transmitting immune-mediated repression of the gonadotropic axis during acute inflammation, and yet key facets of such a phenomenon remain ill defined. Using lipopolysaccharide S (LPS)-treated male rats as model of inflammation, we document herein the pattern of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin-IR in the arcuate nucleus (ARC) that was not observed under conditions of metabolic stress induced by 48-h fasting. In addition, absolute responses to kisspeptin-10 (Kp-10), in terms of LH and testosterone secretion, were significantly attenuated in LPS-treated males that also displayed a decrease in food intake and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key center for the neuroendocrine control of reproduction. Our results also suggest that suppressed gonadotropic function following inflammatory challenges might involve a reduction in absolute responsiveness to kisspeptin that is independent of the anorectic effects of inflammation. Kiss1/kisspeptins; gonadotropin-releasing hormone; gonadotropins; lipopolysaccharide S doi: 10.1152/ajpendo.00081.2010.

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. KiSS-1; G protein-coupled receptor 54; gonadotropin-releasing hormone; constant infusion; fasting; leptin; puberty; luteinizing hormone; follicle-stimulating hormone doi: 10.1152/ajpendo.90240.2008.

For rodents that live underground, digging in highly compacted soils requires a higher energy expenditure than digging in poorly compacted soils. We tested how soil hardness affects the bite force as well as the shape and size of the skulls and mandibles of tuco-tucos. Our hypothesis is that species that inhabit harder soils would show a stronger bite force, which should be reflected in the shape of the skull and mandible, while species living in softer soils should have a weaker bite force. We used 24 species of the genus Ctenomys to estimate bite force (through the incisor strength formula) and quantify the shape and size of the skull and mandible. Information on soil bulk density in the regions occupied by each species was obtained from the literature. We used a combination of geometric morphometric and comparative methods to test our hypothesis. A phylogenetic linear regression ( PGLS) between bite force (N) and centroid size was used to account for the dependence of bite force on size. We employed a series of two-block partial least-squares analyses to uncover the covariation between bite force and the shape of the skull and mandible. Finally, we ran five independent PGLS analyses to assess the influence of bulk density on bite force, skull shape and mandible shape, taking into account phylogenetic non-independence. Species with higher bite forces tend to inhabit more-compact soils. However, for most species, the relationship between bite force and soil bulk density was unclear, resulting in a low overall correlation. Nonetheless, differences in skull and mandible shapes were generally associated with bite force ( r = 0.60). In denser soils, species with high and low bite forces occur, whereas in lower density soils, we found only species with weak bite forces. Differences in the excavation strategies among species may be responsible for this pattern. [ABSTRACT FROM AUTHOR]