The bilevel chamber revealed differential involvement of vasopressin and oxytocin receptors in female mouse sexual behavior.

Arginine vasopressin (AVP) and oxytocin (OT) are well-known as neuropeptides that regulate various social behaviors in mammals. However, little is known about their role in mouse female sexual behavior. Thus, we investigated the role of AVP (v1a and v1b) and OT receptors on female sexual behavior. First, we devised a new apparatus, the bilevel chamber, to accurately observe female mouse sexual behavior. This apparatus allowed for a more precisely measurement of lordosis as receptivity and rejection-like behavior (newly defined in this study), a reversed expression of proceptivity. To address our research question, we evaluated female sexual behavior in mice lacking v1a (aKO), v1b (bKO), both v1a and v1b (dKO), and OT (OTRKO) receptors. aKO females showed decreased rejection-like behavior but a normal level of lordosis, whereas bKO females showed almost no lordosis and no change in rejection-like behavior. In addition, dKO females showed normal lordosis levels, suggesting that the v1b receptor promotes lordosis, but not necessarily, while the v1a receptor latently suppresses it. In contrast, although OTRKO did not influence lordosis, it significantly increased rejection-like behavior. In summary, the present results demonstrated that the v1a receptor inhibits proceptivity and receptivity, whereas the v1b and OT receptors facilitate receptivity and proceptivity, respectively.

Extracellular sodium regulates fibroblast growth factor 23 (FGF23) formation.

The bone-derived hormone fibroblast growth factor-23 (FGF23) has recently received much attention due to its association with chronic kidney disease and cardiovascular disease progression. Extracellular sodium concentration ([Na+]) plays a significant role in bone metabolism. Hyponatremia (lower serum [Na+]) has recently been shown to be independently associated with FGF23 levels in patients with chronic systolic heart failure. However, nothing is known about the direct impact of [Na+] on FGF23 production. Here, we show that an elevated [Na+] (+20 mM) suppressed FGF23 formation, whereas low [Na+] (-20 mM) increased FGF23 synthesis in the osteoblast-like cell lines UMR-106 and MC3T3-E1. Similar bidirectional changes in FGF23 abundance were observed when osmolality was altered by mannitol but not by urea, suggesting a role of tonicity in FGF23 formation. Moreover, these changes in FGF23 were inversely proportional to the expression of NFAT5 (nuclear factor of activated T cells-5), a transcription factor responsible for tonicity-mediated cellular adaptations. Furthermore, arginine vasopressin, which is often responsible for hyponatremia, did not affect FGF23 production. Next, we performed a comprehensive and unbiased RNA-seq analysis of UMR-106 cells exposed to low versus high [Na+], which revealed several novel genes involved in cellular adaptation to altered tonicity. Additional analysis of cells with Crisp-Cas9-mediated NFAT5 deletion indicated that NFAT5 controls numerous genes associated with FGF23 synthesis, thereby confirming its role in [Na+]-mediated FGF23 regulation. In line with these in vitro observations, we found that hyponatremia patients have higher FGF23 levels. Our results suggest that [Na+] is a critical regulator of FGF23 synthesis.

Neural and Hormonal Basis of Opposite-Sex Preference by Chemosensory Signals.

In mammalian reproduction, sexually active males seek female conspecifics, while estrous females try to approach males. This sex-specific response tendency is called sexual preference. In small rodents, sexual preference cues are mainly chemosensory signals, including pheromones. In this article, we review the physiological mechanisms involved in sexual preference for opposite-sex chemosensory signals in well-studied laboratory rodents, mice, rats, and hamsters of both sexes, especially an overview of peripheral sensory receptors, and hormonal and central regulation. In the hormonal regulation section, we discuss potential rodent brain bisexuality, as it includes neural substrates controlling both masculine and feminine sexual preferences, i.e., masculine preference for female odors and the opposite. In the central regulation section, we show the substantial circuit regulating sexual preference and also the influence of sexual experience that innate attractants activate in the brain reward system to establish the learned attractant. Finally, we review the regulation of sexual preference by neuropeptides, oxytocin, vasopressin, and kisspeptin. Through this review, we clarified the contradictions and deficiencies in our current knowledge on the neuroendocrine regulation of sexual preference and sought to present problems requiring further study.

Why does castrated male odor attract sexually active male rats?-Attractivity induced by hypothalamus-pituitary-gonad axis block.

Sexually experienced male rats show an olfactory preference for estrous female odor compared to male odor. Notably, they also prefer castrated male over gonadally intact male odor. This study examined the role of elevated circulating gonadotropins and gonadotropin-releasing hormone (GnRH) induced by disinhibition of the hypothalamus-pituitary-gonad axis in the castration-induced attractiveness of male rats. Experiment I compared preference of sexually experienced males between odors of castrated males injected with a GnRH antagonist (Cast+Ant), castrated males injected with saline (Cast), and gonadally intact males (Sham). These olfactory preference tests revealed that probe males significantly preferred Cast over Sham and Cast+Ant odors but had no preference between Sham and Cast+Ant odors. Experiment II used hypophysectomy (HPx) to remove the gonadotropin source in place of pharmacologically antagonizing GnRH. Similarly, the probe males preferred Cast (high both GnRH and gonadotropins) over HPx (high GnRH but no gonadotropin) odors, but also preferred HPx than Sham (low both GnRH and gonadotropins) odors. We then examined the effects of exogenous gonadotropins, human chorionic gonadotropin (hCG) and equine chorionic gonadotropin (eCG), to reveal which gonadotropins critically affect on the attractiveness of HPx males. The olfactory preference tests revealed that injecting eCG, but not hCG, significantly increased the probe males` preference compared to HPx male odor, suggesting that the attractiveness is augmented via follicle stimulating hormone (FSH) receptor rather than luteinizing hormone receptor. These results indicate that sexually active male rats show olfactory preference for castrated male rats due to elevated GnRH and FSH blood levels produced by a lack of androgens.