Further Evidence on the Intrahypothalamic Locus for Androgenization of Female Rats

Nadler, Ronald D.

doi:10.1159/000122160

Cited by 31 publications

(3 citation statements)

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“…progestin receptor induction and changes in various enzyme activities (see 58). Within the developing rodent brain, estrogen-concentrating hypothalamic sites are implicated in brain sexual differentiation by the efficacy of micro-implants of testosterone propionate and estradiol in this region (17,28,69,70) and by the demonstration that neurite outgrowth induced by estradiol in organ cultures of neonatal mouse hypothalamus emanates from estrophilic neu rons (92). However, because many neurons project outside their immediate brain region, it is conceivable and in fact likely that some steroid effects may be manifested at the synaptic endings of a nonestrophilic brain area even though the primary site of action is an estrophilic region (60).…”

Section: Concluding Remarks: Actions Of Gonadal Steroids On Neural Anmentioning

confidence: 99%

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

McEwen¹

1980

Annu. Rev. Physiol.

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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...

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Section: Concluding Remarks: Actions Of Gonadal Steroids On Neural Anmentioning

confidence: 99%

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

McEwen¹

1980

Annu. Rev. Physiol.

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“…PK was significantly elevated in the lateral preoptic and suprachiasmatic nuclei of the anterior hypothalamus and also in the medial mamillary nucleus and median eminence. No significant changes occurred in PFK activity.Since the phenomenon of androgen sterilization was initially described [Barraclough, 1961;Bradbury, 1941; P feiffer, 1936] 1973/1974; M en n in et al, 1974], and the hypothalamic locus thought to mediate the androgen effect [Barraclough, 1966; Barraclough and G o r sk i, 1961; G o r sk i, 1966;G orski and Barraclough, 1963; N adler, 1971, 1972, 1973 have been made. Changes in the overall metabolism [L ibertu n et al, 1969; M o g u ilevsky and R u b in stein , 1967; M ogu ilevski et al, 1969;Scacchi et al, 1973], specific enzyme steps [G a z ir i and Ladosky, 1973; H u n t er and…”

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confidence: 99%

Quantitative Histochemical Studies of the Hypothalamus. Control Point Enzymes Following Androgen Sterilization

Packman¹,

Bragdon²,

Boshans³

1977

Neuroendocrinology

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Three control point enzymes of the Embden-Meyerhof pathway, hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) were measured by quantitative histochemical methods in individual hypothalamic nuclei of adult neonatally androgenized female rats. HK activity was significantly increased in anterior hypothalamic nuclei: medial preoptic, lateral preoptic, and suprachiasmatic. PK was significantly elevated in the lateral preoptic and suprachiasmatic nuclei of the anterior hypothalamus and also in the medial mamillary nucleus and median eminence. No significant changes occurred in PFK activity.

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“…Since both the pituitary gland and ovaries from adult female rats injected with androgen in early infancy can function normally when transplant ed into an untreated host (Harris, 1970), it is believed that the permanent effects of neonatal androgen lie within the central nervous system. From testosterone implants in the brain, Nadler (1972Nadler ( , 1973 and Hayashi and Gorski (1974) have shown that the androgen acts primarily on the hypothalamus within the preoptic and ventromedial-arcuate areas. Barraclough (1968) has suggested that the androgen may produce functional changes in the suprachiasmatic-preoptic areas of the hypothalamus, which are necessary for cyclic gonadotropin release prior to ovulation in the female rat.…”

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confidence: 99%

Effect of Neonatal Androgen on the Activity of Peptidases in the Rat Brain Inactivating Luteinizing Hormone-Releasing Hormone

Griffiths¹,

Hooper²,

Jeffcoate³

et al. 1976

Horm Res

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The activity of peptidase enzymes in different brain areas inactivating luteinizing hormone-releasing hormone (LH-RH) was investigated in normal male and female rats and female rats treated neonatally with androgen. Of the two fractions containing peptidase activity, changes were found only in the supernatant (soluble/cytoplasmic) fraction and were restricted to the hypothalamus and cortex. In both these brain areas, peptidase activity was considerably higher in androgen-treated than in normal female rats; there was no significant difference between activity in male rats and the androgen-treated female rats. These findings indicate that neonatal androgen produces masculinization of the mechanisms responsible for LH-RH inactivation in the hypothalamus which may reflect changes observed elsewhere in gonadotropin secretion in androgen-treated female rats. The changes in peptidase activity in the cortex may infer that sexual differentiation of the brain under the influence of androgen is not limited to the hypothalamus and can be manifested at extrahypothalamic sites within the central nervous system.

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Further Evidence on the Intrahypothalamic Locus for Androgenization of Female Rats

Cited by 31 publications

References 10 publications

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

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

Quantitative Histochemical Studies of the Hypothalamus. Control Point Enzymes Following Androgen Sterilization

Effect of Neonatal Androgen on the Activity of Peptidases in the Rat Brain Inactivating Luteinizing Hormone-Releasing Hormone

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