The effect of castration alone or castration and subsequent administration of testosterone propionate to males or estradiol benzoate (EB) to females on the content and distribution of gonadotropin-releasing hormone (GnRH) in the median eminence and organum vasculosum of the lamina terminalis (OVLT) was studied in rats and mice. Specimens were labeled with the peroxidase-antiperoxidase method of imrnunocytochemistry using an antiserum to synthetic GnRH conjugated to bovine serum albumin. Five weeks after castration, the content of immunoreactive GnRH in the median eminence of rats and mice of both sexes was markedly depleted. The reduction in GnRH stores was most obvious in axons and nerve endings in the middle and caudal regions of the median eminence. Replacement therapy with gonadal steroids reversed the castrationinduced reduction in GnRH content. EB failed to completely restore GnRH in the median eminence of ovariectomized mice to control levels, but otherwise there were no differences in the effectiveness of replacement therapy with respect to sex or species. None of the experimental treatments had any effect on the distribution or content of GnRH associated with the OVLT.These observations suggest that: 1) after removal of the negative feedback action of gonadal steroids, there is an increased level of secretory activity by GnRH-producing neurons ending in the median eminence; 2) testosterone propionate in orchidectomized males and EB in ovariectomized females return the elevated secretory rate of such neurons to levels similar to those in intact control animals; and 3) GnRH neurons ending in the OVLT may not be directly involved in the negative feedback control of gonadotropin secretion. {Endocrinology 106: 1442, 1980)
Since differential chemical staining has been unsatisfactory for demonstration of specific secretory cell types in the hypophyseal pars distalis of the mouse, the objective of this study was to determine whether the peroxidase-antiperoxidase immunocytochemical procedure might be more effective. Accordingly, representative sections from the hypophyses of 17 female and 15 male adult mice of the Swiss-Webster strain were immunostained, 16 antisera to 5 pituitary hormones or their subunits being utilized. Five secretory cell types were demonstrated. Somatotropes were ovoid to spheroidal and distributed quite generally in the gland except for the "sex zone" where they were scarce. Somatotropes were larger and more numerous in the male than in the female. Mammotropes were polyhedral and also generally distributed in the gland except for the "sex zone" where few were observed. Mammotropes were larger and more numerous in the female than in the male. Corticotropes were small, stellate and few. They were most common near the ventral surface of the gland and formed bilateral centromedial groups in the lateral wings. Thyrotropes were usually large and polyhedral. They were restricted almost solely to the ventral region of the pars distalis. Gonadotropes were polyhedral, and generally distributed, except for aggregation in the cephalomedian "sex zone." Most gonadotropes appeared to contain both luteinizing hormone and follicle-stimulating hormone. Thus, all secretory cell types recognized in other species can be demonstrated readily in the mouse hypophysis with immunocytochemistry.
Growth hormone-release-inhibiting hormone (somatostatin) has been localized in several central nervous system sites, but the contribution of somatostatin in these various loci to the control of growth hormone (GH) production is unclear. In the present study, the efficacy of castration, alone, or with subsequent gonadal steroid administration, in modulating hypophysial GH production was examined, and the response of somatostatin-containing nerve endings in the median eminence and the organum vasculosum of the lamina terminalis (OVLT) was evaluated by means of immunocytochemistry. Orchidectomy reduced the size and number of immunoreactive GH-cells, and testosterone administration prevented this change. Ovariectomy appeared to stimulate the somatotropes, but this effect was neither as dramatic nor as consistent as the effect of castration in the male. Administration of estradiol, however, resulted in a marked reduction in the number, size, and GH content of somatotropes in all animals examined. Somatostatin was localized in the ext.erne1 lamina of the median eminence and in nerve endings surrounding the core of capillaries in the OVLT. Only the median eminence responded to steroid manipulations with a visible change in the immunoreactive pool of somatostatin, with a decrease following orchidectomy, which was reversible by testosterone treatment, and an increase following ovariectomy, which was reversible by estradiol treatment. However, as in the GH responses to steroid manipulations, the somatostatin responses were more variable in females than in males.These results suggest that: 1) testosterone promotes and estradiol, a t least at high doses, inhibits storage of GH in the anterior pituitary; 2 ) these changes in GH production may be regulated, in part, by altered somatostatin release from the median eminence into the hypophysial portal blood; and 3) somatostatin in the OVLT may not be involved in the steroid-induced modulation of GH production.Currently available evidence supports the hypothesis that a dual neural regulation of growth hormone (GH) secretion exists. The predominant control is believed to be stimulatory, mediated by a growth hormone-releasing factor (Martin, '76). Although the existence of this releasing factor is supported by considerable experimental evidence, its isolation and characterization have not been achieved; thus, specific techniques for its localization and measurement can not yet be applied. The inhibitory control is thought to be mediated by growth hormone-release-inhibiting hormone, or somatostatin, which has been isolated, char. acterized, and synthesized (Brazeau et al., '73). Using both radioimmunoassay (Brownstein e t al., '75; Epelbaum e t al., '77; Kobayashi et al., '77; Pate1 and Reichlin, '78) and immunocytochemistry (see Zimmerman, '77; Elde e t al., '78 for reviews), somatostatin has been localized in several central nervous system sites, including both hypothalamic and extrahypothalamic areas. There appear to be several general patterns of somatostatin localizatio...
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