Showing papers by "Bruce S. McEwen published in 1976"

Autoradiographic localization of hormone-concentrating cells in the brain of the female rhesus monkey.

Abstract: With autoradiographic procedures, cells which bind 3H-estradiol were found in preoptic, hypothalamic and limbic structures in the brains of ovariectomized, adult female rhesus monkeys. Estrogen-binding cells were seen in the medial preoptic area, medial anterior hypothalamus, ventromedial nucleus, and especially heavy labelling was seen throughout the extent of the arcuate (infundibular) nucleus of the hypothalamus. In limbic structures, cells in the bed nucleus of the stria terminalis and in the medial nucleus of the amygdala were well labelled. Systematic charting also revealed smaller numbers of estrogen-concentrating cells in other specific hypothalamic and limbic locations. In the anterior pituitary, significant numbers of basophils and acidophils were found to bind estrogen. Pars intermedia and the posterior lobe were virtually unlabelled. In the uterus, heavily labelled cells were seen in the endometrial stroma and in the myometrium. These autoradiographic findings agree with results of parallel biochemical experiments. In monkeys injected with 3H-corticosterone, the most extensive high-intensity binding found with autoradiography was in the hippocampus. Both pyramidal neurons and dentate gyrus granule cells were labelled. Biochemical experiments, also, showed highest cell nuclear accumulation of corticosterone in the hippocampus. Findings with estradiol in the rhesus monkey extend to primates conclusions based on autoradiographic experiments with steroid sex hormones in a wide variety of vertebrates, including fish, amphibians, birds, and various mammalian species (Morrell et al., '75a). All of these vertebrate forms have sex hormone-concentrating neurons, which are found in specific preoptic, hypothalamic and limbic structures. In the species studied, such hormone-concentrating neurons appear to be involved in the hormonal control of behavioral and pituitary function.

Interactions between hormones and nerve tissue.

Abstract: The interactions between steroid hormones particularly sex hormones and nerve tissue are discussed. Steroid hormones act on the genetic material of the cell nucleus. Estradiol is responsible for the reversible activation of the lordosis response and ovulation in adult female rats. When certain areas of the developing brain are exposed to hormones such as estradiol permanent structural changes in the brain lead to a male pattern of behavior in the adult. if the developing rat male brain is deprived of testosterone female behavior results. These differences are probably due to the state of differentiation of the neurons at the time of hormonal interaction. The nerve cell circuits which may be established by steroid hormone stimulation during sexual differentiation of the brain become permanent and are not susceptible to further hormonal influence. Rather the hormones affect the functional efficacy of the circuits. Further research is needed to understand the chemical properties of the target neurons necessary for sexual behavior response.

Early response of rat brain tryptophan hydroxylase activity to cycloheximide, puromycin and corticosterone

Abstract: — The activity of tryptophan hydroxylase was measured in whole homogenates of midbrain and forebrain areas of the rat brain. A significant elevation of tryptophan hydroxylase in midbrain and forebrain was found within 1 h after injection of corticosterone hemisuccinate Na salt (10mg/kg) into normal rats. A further elevation of tryptophan hydroxylase at 4 h after injection occurred only in the midbrain region. A rapid alteration of tryptophan hydroxylase was also observed following intracistemal injection of a protein synthesis inhibitor, cydoheximide. A significant depression of 50% of normal levels occurred both in midbrain and forebrain regions within 1 h. However. 4 h after injection only the midbrain tryptophan hydroxylase level was depressed, and this depression was 16% of normal levels. This temporal and spatial pattern following cydoheximide injection was not the result of changes in the ability of cydoheximide to inhibit in vivo protein synthesis since [3H]valine incorporation into protein was shown to be equally depressed at both 1 and 5 h in both the midbrain and forebrain. Puromycin blocked [3H]valine incorporation into proteins in the midbrain and forebrain. but only caused a depression of 16% of tryptophan hydroxylase in the midbrain at 4 h. The aminonucleoside derivative of puromycin has no effect on protein synthesis or on tryptophan hydroxylase. Cydoheximide had no effect on tryptophan hydroxylase in vitro. The data suggest that cydoheximide and corticosterone produce an early (1 h) effect on tryptophan hydroxylase unrelated to de novo protein synthesis in regions known to contain perikaryon (midbrain) and axon terminals (forebrain) of 5-HT-containing neurons. The later (4h) effects of these two compounds and puromycin on tryptophan hydroxylase in the perikaryon (midbrain) region of 5-HT-containing neurons probably result from alteration in de novo protein synthesis. The half time of tryptophan hydroxylase in midbrain region is calculated to be 12 h.

Interactions of testosterone and estradiol with the neonatal rat brain : protective mechanism and possible relationship to sexual differentiation

Abstract: This paper summarizes recent work from this laboratory concerning the interaction of radioactive testosterone and various estrogens with brains of newborn rats. Testosterone7-3H is shown to be converted in vivo to estradi Ol7-3Hand this product is retained by cell nuclei in hypothalamus and limbic structures to a degree which points to the existence of putative estrogen receptor sites in the neonatal brain. This inference has been verified by in vivo studies using 3H-estradiol, 3H-diethylstilbastrol (DES) and 3H-II(3-methoxy I7 oc-ethynyl 17 (3-estradiol (RU 285) Cell nuclear retention of radioactive estrogens is prevented by non-radioactive 17(3-estradiol and i7a-estradiol and by the non-steroidal anti-estrogen CI6 28, and is not significantly reduced by a variety of non-radioactive 5a-reduced androgens or by progesterone. Cell nuclear labeling is substantial in hypothalamus, amygdala, preoptic area, and much lower in cerebellum and midbrain and brainstem. Cerebral cortex is noteworthy because it lacks significant aromatization capability and yet retains 3H-estrogens in a manner similar in specificity and intensity of labeling to hypothalamus, amygdala and preoptic area. The developmental changes of estrogen binding capacity are described. The neonatal brain and blood also contains another estrogen binding protein (fEBP-fetoneonatal estrogen binding protein) which binds 3H-estradiol but to a far lesser extent binds synthetic estrogens like 3H-DES and 3H-RU 285. The ability of 3H-estrogens to bind in vivo to cell nuclear receptor sites appears to be inversely related to their binding to fEBP. Hence, the protective role for this fEBP against potentially deleterious effects of estradiol17 Pis strongly supported, and the potential dangers of certain synthetic estrogens are once again demonstrated. The relationship of these results to the process of sexual differentiation is discussed.