Binding and Metabolism of Sex Steroids by the Hypothalamic-Pituitary Unit: Physiological Implications

Abstract

INTRODUCTION +1256During the past decade, putative receptor systems for sex steroid hormones have been identifi ed, characterized, and anatomically mapped in the brains and pituitary glands of representative vertebrate species. This information has been obtained by three techniques: (a) steroid autoradiography after in vivo 3H-steroid administration (36,68), and (b) in vitro receptor assays as well as (c) in vivo 3H-steroid administration and cell nuclear isolation, both performed on dissected pieces of brain tissue (54). Neural steroid receptors appear to be similar, if not identical, to receptor systems from nonneural target tissues. Their mode of action, implied by their similarity to peripheral receptors, is presumed to be at the level of gene expression and regulation of genomic activity.Principal interest in these receptors now centers around relating their neuroanatomical location and their occupation by endogenous and exoge nous steroids to neuroendocrine and behavioral effects of the hormones. More broadly speaking, research on steroid hormone action in brain and pituitary is now directed toward finding and describing the hormone initiated chemical and cellular processes that underly these neuroendocrine and behavioral events. The location of steroid receptors is a useful though not infallible guide in deciding where in the brain to look. (Steroid effects may exist that do not involve these receptors. This matter is considered in the Concluding Remarks.) Here I review gonadal steroid metabolism, recep tor localization, and approaches to the study of receptor involvement in brain function. 97 Further ANNUAL REVIEWS 98 McEWEN RECEPTOR LOCALIZATION IN RELATION TO STEROID METABOLISM AndrogensReceptors for androgens have been characterized in rat and mouse brain and pituitary tissue (see 55, 58). The specificity of steroid binding and the physicochemical properties (6-7S in low salt and 3-4S in high ionic strength buffer after sucrose density gradient sedimentation) are similar to those of prostate androgen receptors. Androgen receptors are absent in brain and pituitary tissue of rats and mice bearing the X-linked testicular feminizing (Tfm), or androgen insensitivity, mutation (5, 26,71). The neuroanatomical distribution of androgen receptors has been characterized for rats and mice by autoradiography (81,84,85) and by biochemical analysis (8, 15, 43). Androgen receptors, found throughout the brain, are concentrated in pitui tary, hypothalamus (H), septum, preoptic area (P), and amygdala (A). Only one receptor seems able to recognize both testosterone (T) and 5a-dihy drotestosterone (5a-DHT) (27).Two aspects of T metabolism are crucial to receptor occupation: aromati zation to estradiol (44, 72) and .6. 4-5 reduction to 5a-or 5,B-DHT and related androstanediols (55). Sa-reductase activity occurs throughout the rat brain and pituitary and does not seem to be a limiting factor in androgen receptor occupation (cf 22, 44). Aromatization is absent from pituitary and from cerebral cortex and is present in H, P, an...

Some rewarding effects of androgens may be mediated by actions of its 5α-reduced metabolite 3α-androstanediol

“…Connolly, Roselli, and Resko (1990) have demonstrated that adult male guinea pig brains contained higher quantities of androgen aromatase than female brains. Androgen aromatase is concentrated in the limbic system and hypothalamus (amygdala, preoptic area, septum, hippocampus, and medial basal hypothalamus), whereas low levels were consistently found in cortical tissue (McEwen, 1980). Furthermore, female rats treated with T show a more marked enhancement of social aggression than rats treated with the nonaromatizable androgen dihydrotestosterone (DHT).…”

The Possible Role of Androgenic Hormones in Maturation of Alpha2‐Adrenergic Mechanisms in the Rat

“…In the adult rat testosterone could modulate the phasic release of somatostatin (14) and it is an essential component in the expression of the male GH secretory pattern Recently we found that the GH-releasing and hypotensive action of clonidine were lost in long-term castrated rats. These effects have been restored by testosterone replacement of the castrates (1 6).…”

Effet des androgènes sur l’activité sportive

“…Ainsi le nucleus des r6gions pr6 optiques est plus volumineux chez les rats males [7] et la portion moyenne du noyau de l'amygdale m6diane est 6galement plus 61ev4e [20]. Le ganglion sympathique cervical sup4rieur est plus grand [18]. La testost6rone est capable d'augmenter le facteur de croissance nerveuse [3] conduisant ~ une augmentation de la survie neuronale [10].…”

“…La testost6rone est capable d'augmenter le facteur de croissance nerveuse [3] conduisant ~ une augmentation de la survie neuronale [10]. Ces actions paraissent s'expliquer par une concentration 41ev6e de r6cepteurs aux androg6nes dans l'hypophyse, l'hypothalamus, la r6gion pr4optique, le septum et l'amygdale [18].…”