Phenotypical segregation among female rat hypothalamic gonadotropin-releasing hormone neurons as revealed by the sexually dimorphic coexpression of cholecystokinin and neurotensin

The neuroendocrine control of the gonad is exerted primarily by the gonadot ropin-releasing hormone neurons located in the septum and the hypothalamus, Despite their sexually dimorphic activity, tonic in males and phasic in fe males, these neurons have not appeared qualitatively different between sexe s in intrinsic organization or chemical phenotype. Here, by using multiple- label immunocytochemistry, it is demonstrated that the phenotype of gonadot ropin releasing hormone neurons is sex specific. In females only, 54.5% of them co-expressed cholecystokinin immunoreactivity and 29.4% additionally e xpressed neurotensin immunoreactivity. These multipeptidergic neurons were observed in the hypothalamus but not in the septum. During postnatal develo pment, cholecystokinin and neurotensin immunoreactivities were first detect ed in gonadotropin-releasing hormone-containing axons of the median eminenc e at vaginal opening, suggesting an involvement of the neuropeptides in per i-ovulatory events. This peptidergic phenotype was not apparent in females ovariectomized as adults but was reinstated by estradiol treatment, In adul t males, the testicle does not control this phenotype because orchidectomiz ed adults did not display it, whatever the postoperative delay (one to five weeks) or substitutive chronic steroid treatment (testosterone or estradio l). The testicle may, however, masculinize the phenotype neonatally because estradiol or testosterone treatment in adulthood induced an expression of cholecystokinin immunoreactivity in gonadotropin-releasing hormone-containi ng axons of the median eminence in both males and females that were gonadec tomized at birth. This procedure, however, failed to significantly induce a n expression of neurotensin immunoreactivity, suggesting a role of the post natal ovary on this element of the chemistry of gonadotropin-releasing horm one neurons. Thus, the gonad permanently organizes the gonadotropin-releasing hormone ne uronal population, resulting, at least in females, in a mosaic of phenotypi cally distinct, functional subunits. (C) 2000 IBRO. Published by Elsevier S cience Ltd. All rights reserved.