Paula G. Davis

Steroid hormones: humoral signals which alter brain cell properties and functions.

Publisher Summary The steroid hormones influence the brain to affect behavior. This chapter discusses the intracellular steroid receptors in neural tissue; their anatomical distribution and properties, their role in carrying hormone to the cell nucleus, and their effects upon gene expression. It also describes the direct effects of steroids upon neural tissue which do not appear to be mediated by intracellular steroid receptors. It provides a more integrated picture of how steroid hormones influence patterns of behavior during the development and in adult life, using as an example the effects of estradiol in the rat brain. The brain contains receptor sites for all five classes of steroid hormones. Brain regions that contain such cytosol steroid receptors also display translocation of labeled hormone to the cell nuclear compartment, and this phenomenon underlies autoradiographic localization of steroid hormone concentrating cells, because the presence of label over the cell nucleus provides a visually striking and quantifiable endpoint. Cell nuclear translocation of steroid hormones in neural tissues is not necessarily accompanied by the extensive cytosol receptor depletion even when nuclear sites are loaded to capacity. There are other, indirect demonstrations of genomic involvement in steroid action in the brain.

Application of anisomycin to the lateral ventromedial nucleus of the hypothalamus inhibits the activation of sexual behavior by estradiol and progesterone

Abstract The protein synthesis inhibitor, anisomycin blocked the activation of feminine sexual behavior in rats when applied directly to the lateral portion of the ventromedial hypothalamic nucleus. This supports the idea that estradiol and progesterone activate sexual behavior by inducing the synthesis of specific proteins in target cells of the ventromedial nucleus.

In vitro measurement of cytosol and cell nuclear androgen receptors in male rat brain and pituitary

An in vitro assay procedure is described for measuring androgen receptor binding in cytosol and cell nuclei of brain and pituitary tissue using [3H]R1881 as ligand. The cell nuclear assay uses the exchange method, which permits assessment of endogenous occupancy of androgen receptors in brain and pituitary. Competition and saturation analysis indicated that [3H]R1881 binding has the specificity and nanomolar affinity expected of an androgen receptor. Moreover, we demonstrated that androgen receptor binding predominated in cytosol from castrated rats and in cell nuclei of male rats treated in vivo with testosterone. Furthermore, as expected, testicular feminized male rats showed low levels of putative androgen receptors in both cytosol and cell nuclei.

Independence of the differentiation of masculine and feminine sexual behavior in rats

Abstract Male rats received Silastic implants of the aromatase inhibitor, 1,4,6-androstatriene-3, 17-dione (ATD), on days 2–10 of life. Controls received blank implants. There were no differences in the masculine sexual behavior of ATD and control males when they were tested as gonadally intact adults. In contrast, even without exogenous hormone treatment, nine of 14 ATD males exhibited lordosis behavior, whereas only one of 12 controls did so. In addition, during a sexual preference test in which access was provided to both a sexually receptive female and to a stud male, there was no difference in the proportions of ATD ( 11 14 ) and control ( 7 12 ) males that copulated with the stimulus female; however, seven of the ATD males also exhibited feminine sexual behavior including some instances of solicitation. Only one of the control males showed any lordosis behavior. In general, all animals spent more time with the stimulus female than with the stud male. At the termination of preference testing, all animals were castrated and then tested twice for feminine sexual behavior under exogenous estradiol benzoate and progesterone. All of the ATD males showed lordosis behavior with a mean lordosis quotient (LQ) of 85; and 11 of the 14 also showed solicitation behavior. Only five of 12 control males exhibited lordosis ( X LQ = 59 ) and only one showed solicitation behavior. These results indicate that the propensity of males to show feminine sexual behavior can be manipulated independently of the capacity for masculine sexual behavior. Moreover, our results suggest that the process of defeminization may occur primarily postnatally in rats since treatment during that period results in substantial increments in later feminine sexual behavior including solicitation behaviors.

Attenuating the defeminization of the neonatal rat brain: Mechanisms of action of cyproterone acetate, 1,4,6-androstatriene-3,17,-dione and a synthetic progestin, R5020

Abstract Although defeminization of the rat brain appears to depend significantly on the conversion of testosterone (T) to estradiol (E2), the antiandrogenic steroid cyproterone acetate (CA) is able to attenuate defeminization. In order to study the mechanism of action of CA on brain sexual differentiation, newborn male rats were given subcutaneous injections of this steroid on postnatal Days 2–6. When castrated on Day 70 and given estrogen and progesterone, these CA-treated males displayed elevated lordosis quotients (LQ) compared to controls. CA-treated neonatal males were also examined at the end of the drug treatment to ascertain the mechanism of drug action: (1) Serum T levels were normal; (2) Brain cell nuclear estrogen receptor occupation, estimated by an exchange assay, was reduced by ≈ 30% in the brains of the CA-treated males, although the ability of exogenous E2 to occupy these brain estrogen receptors was not reduced. Other work has demonstrated a weak competitive effect of cyproterone on aromatization, and thus cyproterone acetate may have interfered with the conversion of T to E2 CA also has progestogenic activity, and 5-mm capsules of a potent synthetic progestin, R5020, given to newborn male rats on Days 2–6, are shown to elevate the LQ after postnatal Day 70 to the same extent as CA. However, R5020 did not reduce estrogen receptor occupation in the neonatal male rat brain and was without effect on serum T levels in the neonatal male. Because of the implied role of T-derived estrogens in defeminization, an experiment was conducted showing that the defeminizing action of estradiol benzoate given to 3-day-old female rat pups is attenuated by the antiestrogen, CI628, and not by the potent inhibitor of aromatization, 1,4,6-androstatriene-3,17-dione (ATD). This result complements previous experiments showing that both ATD and CI628 attenuate the defeminization produced by T. Taken together, the results lend further support to a pivotal role for aromatization and for estrogen-receptor interactions in the defeminizing effects of T. The actions of progestins such as CA and R5020 in attenuating defeminization are discussed in relation to the recent demonstration of progestin receptors in the neonatal rat brain. It is concluded that CA may act by a combination of actions, both by inhibiting aromatization and by acting as a progestin.