Sex differences in mammalian and chicken-II gonadotropin-releasing hormone immunoreactivity in musk shrew brain.

Many vertebrates have more than one molecular form of gonadotropin-releasing hormone (GnRH) present in brain. In all cases documented to date, GnRH neurons located in the forebrain are critical players in the brain-pituitary-gonadal feedback axis although the details of how steroids regulate GnRH remain elusive. The function of the second form, usually produced in cells in the midbrain, is not known. It has been hypothesized that this GnRH acts as a neurotransmitter. In the musk shrew (Suncus murinus), as in other mammals, the forebrain cells produce mammalian GnRH (mGnRH) and chicken-II GnRH (cGnRH-II) is present in midbrain neurons. Immunocytochemical analyses were performed to examine sex differences and determine whether the presence or absence of the gonads had any affect on cell number and/or fiber area in the major terminal fields of both forms of GnRH. We detected a significant sex difference in the numbers of immunoreactive (ir) neurons containing mGnRH and cGnRH-II. In both GnRH systems, males have significantly more GnRH-ir cells than females. Furthermore, ovariectomy significantly increased the number of mGnRH-ir and cGnRH-II-ir cell bodies in female brains. In females, changes in the size of the immunoreactive fiber area of the medial habenula were identical to those noted for cGnRH-II cells. In males, the major terminal field for the mGnRH fibers was significantly larger in gonad-intact than in castrated males. In sum, ovarian hormones regulate cGnRH-II production and release, as well as some aspects of mGnRH production in neurons. In males, mGnRH fiber area is sensitive to changes in testicular hormones. These data suggest that the phylogenetically conserved cGnRH-II form is regulated by ovarian hormones and, thus, may be involved in the brain-pituitary-gonadal feedback axis.