Bruce Parsons

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.

Androgen receptor levels in hypothalamic and vocal control nuclei in the male zebra finch.

Using a synthetic, non-metabolizable ligand, R1881 (methyltrienolone), an in vitro binding assay was developed to quantify levels of cytosol androgen receptors in microdissected nuclei from the finch brain. Saturable, high affinity binding in the nanomolar range was demonstrated in the brain areas examined, and receptor levels were unaffected by freezing the tissue samples. The assay was specific for androgen receptors when 10 microM triamcinolone acetonide was added to inhibit the binding of R1881 to glucocorticoid and progestin receptors. Levels of cytosol androgen receptors were quantified in 3 hypothalamic and 3 vocal control nuclei presumed to contain high concentrations of androgen receptors on the basis of previous autoradiography. All nuclei examined showed significant levels of androgen receptors ranging from 5.8 to 35.8 fmol/mg protein. Hypothalamic nuclei had higher concentrations than vocal control nuclei.

Temporal relationship between cell nuclear progestin receptor levels and sexual receptivity following intravenous progesterone administration

This study was designed to assess the temporal relationship between the appearance and retention of cell nuclear progestin receptors in hypothalamus and the facilitation and decline of feminine sexual behavior following an i.v. injection of progesterone (P). Nuclear translocation of progestin receptors preceded the earliest appearance of behavior. The behavioral effects of P outlasted the nuclear progestin receptor elevation by several hours. Our results are consistent with the idea that P-induced effects on feminine sexual behavior involve genomic activation.

The effects of long-term estrogen exposure on the induction of sexual behavior and measurements of brain estrogen and progestin receptors in the female rat.

Abstract The purpose of this study was to investigate long-term effects of estradiol-17β (E 2 ) on sexual receptivity and to study the molecular basis for estrogen potentiated changes in receptivity. We therefore examined the long-term effects of E 2 on E 2 and progestin receptors in the hypothalamus-preoptic area-septum (HPS) and pituitary (PIT) of the female rat. Twenty-one days following ovariectomy, females received a 5-mm Silastic capsule of E 2 or cholesterol (C) for 1 week ( pretreatment ). Some animals were sacrificed for chemical analyses (i). The remainder had their capsules removed and 5 days later these animals either were sacrificed for chemical analyses (ii), or received E 2 ( reimplantation ). Forty-six hours after reimplantation, females either were sacrificed for chemical analyses (iii), or were tested for receptivity. When tested with sexually active males or by a manual stimulation method, animals pretreated with E 2 showed significantly better lordosis scores than animals pretreated with C. The tests for lordosis were carried out after administration of E 2 or E 2 + P to all subjects tested. During E 2 pretreatment, HPS and PIT cytosol progestin receptors increased significantly, while available estrogen receptor levels decreased significantly, as compared with C controls. Five days after E 2 pretreatment, HPS progestin receptor levels had decreased to the level observed in C controls, while PIT progestin receptors were slightly elevated. In HPS and PIT, levels of available E 2 receptor in E 2 and C pretreated animals were indistinguishable from each other. Neither the saturation capacity of the estrogen receptor nor the dissociation constant for binding [ 3 H]E 2 was altered by E 2 pretreatment, as shown by Scatchard equilibrium analysis. Forty-six hours following E 2 reimplantation, progestin HPS and PIT receptor levels in E 2 and C pretreated animals were identical. Long-term potentiation of lordosis by E 2 does not result from a change in estrogen or progestin receptor dynamics in HPS of female rats.

Age-related changes in cytoplasmic estradiol receptor concentrations in microdissected brain nuclei: Correlations with changes in steroid-induced sexual behavior

The purpose of this study was to; determine at what age changes in cytoplasmic estradiol receptors are evident in specific microdissected brain areas of the female rat; assess whether alterations parallel previous changes observed when large brain areas were used for determination of receptor concentrations; and assess whether changes in cytoplasmic estradiol receptors are correlated with changes in steroid-mediated physiological functions. To assess the effects of age on cytoplasmic estradiol receptor concentrations, we used virgin female Sprague-Dawley rats at 3-4 months, 7-8 months and 10-11 months of age. They were ovariectomized 7-14 days prior to use to allow maximal translocation of receptors to the cytoplasm. The animals were anesthetized and perfused with a 10% (v/v) solution of dimethylsulfoxide to protect the receptor proteins from the effects of freezing. Brains were removed and frozen. This procedure of freezing the brains caused a minimal (15-18%) loss in the number of receptors and no change in the dissociation constant. Consecutive 300 micron sections were sliced and the following nuclei and brain areas were microdissected: bed nucleus of the stria terminalis, suprachiasmatic-preoptic area, medial preoptic nucleus, periventricular preoptic nucleus, periventricular anterior hypothalamic area, paraventricular nucleus, dorsomedial nucleus, ventromedial nucleus, arcuate-median eminence, medial amygdala, and cortical amygdala. The pituitary gland was also removed and analyzed. The cytoplasmic fraction from a tissue pool from 3 animals was prepared and aliquots were incubated with [3H]estradiol at a final concentration of 1.5 nM in the presence or absence of 100-fold excess moxestrol. Receptor-bound [3H]estradiol was separated from free hormone by gel filtration.(ABSTRACT TRUNCATED AT 250 WORDS)

Progesterone-Like Effects of Estradiol on Reproductive Behavior and Hypothalamic Progestin Receptors in the Female Rat

During the rat estrous cycle, estradiol (E2) and progesterone (P) synergize to activate reproductive behavior. However, receptivity and proceptivity can be elicited by E2 alone in ovariectomized (OVX) animals, particularly when E2 doses are high. The purpose of this study was to determine the neuroendocrine mechanism by which E2 elicits P-dependent reproductive behavior. Adult OVX females received estrogen treatment for 72 h, which consisted of 5 mm Silastic capsules containing 100% E2 or 10% E2, or of 3 injections of estradiol benzoate (EB; 20 micrograms daily). At 72 h, animals were sacrificed for nuclear progestin receptor (NPR) measurements, while others were tested for reproductive behavior. The remaining animals received 1-mg injections of E2, P, moxestrol (Mox) or oil, and either were sacrificed 2 h later for NPR measurements or were tested 4 h later for reproductive behavior. A subset of the animals receiving 1 mg E2 received concurrent administration of the protein synthesis inhibitor, anisomycin (ANI; 100 mg/kg). Acute administration of 1 mg of E2 or P significantly elevated proceptivity, receptivity and NPRs in the mediobasal hypothalamus-preoptic area (MBH-POA) and pituitary (PIT) in females primed with 100% E2. An equivalent dose of Mox was without effect. ANI blocked the acute activation of feminine reproductive behavior by 1 mg of E2. In the absence of acute steroid administration, animals primed for 72 h with EB showed higher levels of reproductive behavior than animals primed with 100% E2.(ABSTRACT TRUNCATED AT 250 WORDS)

Behavioral and Neuroendocrine Effects of Long-Term Progesterone Treatment in the Rat

Progesterone and estradiol, alone or in combination, were administered to ovariectomized rats for 2 weeks. Progesterone alone had no effect on body weight, luteinizing hormone (LH) secretion, receptivity or brain cytoplasmic progestin receptors (CPR). Progesterone in combination with estradiol significantly attenuated estrogen suppression of weight gain and estrogen stimulation of receptivity, the LH afternoon surge and induction of CPR, but did not affect the negative feedback of estrogen on morning LH levels. The decrease in CPR after 2 weeks of progesterone is very similar in magnitude to the decrease observed following acute treatment, suggesting that, unlike neurotransmitter agonists and glucocorticoids, progesterone does not cause down regulation of its receptors in the brain following chronic treatment.