Levels in the Brain of the Stanley-Gumbreck Pseudohermaphrodite Male Rat: Implications for Testosterone Modulation of Neuroendocrine Activity*

Publisher Website
Google Scholar
Abstract
Stanley-Gumbreck pseudohermaphrodite (PSH) and normal littermate (NL) male rats were used to study the intracellular processing of androgens in the brain and anterior pituitary gland. Animals received iv injections of [7-3H]testosterone ([3H]T) or [l,2-3H]5α-dihydrotestosterone ([3H]DHT) and were killed 2 h later to assess cell nuclear concentrations of 3H-labeled androgens and estrogens. Although [3H]DHT was present in cell nuclear preparations from the hypothalamus, preoptic area, and amygdala (HPA), and from the pituitary of NL rats given [3H]DHT injections, little or no radioactivity could be recovered from comparable preparations from PSH rats. After [3H]T injections, markedly different3 H-labeled steroid profiles were obtained when tissue homogenate and nuclear pellet extracts were subjected to chromatographic analysis. In the pituitary, nuclear [3H]T and [3H]DHT levels were 25- and 20 -fold higher, respectively, in NL males than in PSH males. The nuclear levels of these androgens were also significantly higher in brain tissues (i.e. the HPA) of the NL rat. However, in both genotypes, approximately 70% of the recoverable radioactivity in the brain nuclear preparations was associated with estradiol. Furthermore, the nuclear concentrations of this labeled steroid were comparable in PSH and NL rats. Additional studies established that chronic elevations in serum T levels produced comparable increases in estrogen receptor concentrations in nuclear preparations of the HPA of PSH and NL rats. Such findings are consistent with previous in vitro findings that the HPA contains aromatase enzymes capable of converting androgens to estrogens. To determine the physiological significance of the above findings, we monitored the influences of T on several parameters of neuroendocrine function in castrated PSH and NL rats. T administration increased cytosol progestin receptor levels in the preoptic area and hypothalamus in both genotypes and induced lordosis behavior and cyclic LH release when NL and PSH rats were castrated as neonates. Moreover, the frequency of appearance and magnitude of these responses in the PSH rats were comparable or, in some instances, greater than that in the NL rats. In previous pharmacological studies, we have found that each of these T-induced phenomena depend on aromatization and increases in nuclear estrogen receptor levels in the HPA. Significantly, T and estradiol induced lordosis and cyclic LH release in NL and PSH rats castrated on the day after birth but not in rats castrated 8–12 days later. Thus, PSH rats would appear to display yet another alteration in neuroendocrine function previously shown to depend in aromatization: sexual differentiation (defeminization) of the neural circuits controlling female sex behavior and cyclic LH secretion. In marked contrast to the results mentioned above, the ability of T to suppress basal LH release in castrate PSH rats was markedly attenuated when compared to that observed in NL rats. This lack of responsiveness was observed despite serum T levels approximately 3-fold greater than those sufficient to elicit lordosis or cyclic LH secretion. Taken together, the foregoing studies illustrate that a deficiency of functional androgen receptors in the PSH male rat produces some deficits in androgen processing in the brain and pituitary gland. These deficits most likely explain these animals' lack of responsiveness to certain of T's neuroendocrine actions relative to normal males. However, the brain of the PSH rat would appear to possess a “normal” complement of aromatases and estrogen receptors that actively process T under acute or chronic conditions. As a result, the PSH rat is as responsive as normal male siblings to several of the activational and organizational actions of this steroid on brain function.

This publication has 0 references indexed in Scilit: