SAT-004 GnIH Interactions with GnRH-I and -II in Mammalian Brain: Musk Shrews as a Model for Human Reproduction

Abstract Disclosure: G.E. Bentley: None. A. Watanabe: None. H. Ishii: None. I. Sakata: None. S. Aizawa: None. Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that can act in the brain, the pituitary gland, and the gonads to influence reproduction and reproductive behaviors. In the brain, GnIH neurons project to GnRH-I neurons in all vertebrates studied, and GnRH-I neurons express GnIH receptor. In general, GnIH acts to inhibit activity of GnRH-I neurons. Many vertebrates, including humans and non-human primates, additionally express GnRH-II in the brain. GnIH also projects to these GnRH-II neurons, and in birds, GnIH acts on GnRH-II neurons to inhibit sexual activity. However in mammals the functional significance of this neuroanatomical interaction between GnIH and GnRH-II is not clear. The GnRH-II gene is absent or functionally inactivated in many mammals, including rats and mice, making them unsuitable models for studies on the functions of GnRH-II that might be applicable to humans. However, the musk shrew, Suncus murinus, expresses GnRH-II which can modulate food intake and acts as a permissive regulator of female reproductive behavior based on energetic status. In this study, we investigated the relative distributions of GnIH with GnRH-I and -II in musk shrews with the goal of determining whether this species is a tractable model for investigations of the roles of GnIH:GnRH-I and GnRH-II interactions on reproductive physiology and behavior. Using male and female musk shrew brains, we found GnIH immunoreactive (-ir) fibers in putative contact with GnRH-I-ir neurons in the OVLT and pre-optic area, along with putative contact with GnRH-I-ir fibers in the median eminence. Thus, neuroanatomical architecture exists in this species for GnIH to influence GnRH release. In addition, GnIH-II-ir neurons in the midbrain of both sexes receive GnIH-ir fiber input. Thus, based on neuroanatomy, GnIH is likely to influence GnRH-II release and thus sexual behaviors associated with GnRH-II. Presentation: Saturday, July 12, 2025