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At least 523 records · Page 29Linked to original sources
PubMed1990

Effects of day length on sheep neuroendocrine estrogen and progestin receptors.

Gonadal steroid hormone receptors were studied in anterior pituitary, preoptic area, and hypothalamus of ovariectomized ewes. We established that systemic administration of estradiol benzoate elevates levels of nuclear estrogen receptor concentrations and results in the appearance of cytosolic progestin receptor the binding characteristics of which are comparable with that reported in rats and guinea pigs [0.1 nM Kd, binding site density (Bmax) of 111, 22, and 2 fmol/mg protein in pituitary, medial basal hypothalamus, and preoptic area, respectively]. Brain tissues also contained a second, low-affinity progestin binding site. To examine possible effects of photoperiod on neuroendocrine steroid receptors, two groups of sheep were exposed to artificial photoperiods. Ewes experienced alternating periods of long (LD 16:8) or short (LD 8:16) days for 290 days to induce breeding season or anestrous states. Animals were then ovariectomized and given steroid treatments designed to mimic a luteal phase followed by either follicular phase levels of estradiol or withdrawal of all exogenous hormones before determination of neuroendocrine steroid receptor concentrations. Despite the ability of long photoperiods to arrest ovarian cyclicity, magnify negative feedback actions of estradiol upon luteinizing hormone, and reduce the ability of estrogen to trigger behavioral estrus, photoperiod did not influence nuclear estrogen receptor concentrations or the induction of cytosolic progestin receptors in the pituitary, hypothalamus, or preoptic area.

Animals↗
PubMed1996

Effects of food deprivation on induction of neural progestin receptors by estradiol in Syrian hamsters.

Food deprivation, as well as treatment with metabolic inhibitors, suppress steroid hormone-induced estrous behavior in ovariectomized (OVX) Syrian hamsters. Previous work indicates that 48 h of food deprivation decreases the number of detectable estrogen receptor immunoreactive (ERIR) cells in the ventromedial hypothalamus (VMH) and the area just lateral to it (VLH), increases the number of ERIR cells in the medial preoptic area (MPO), and has no effect on the number of ERIR cells in the nucleus of the solitary tract in OVX hamsters. The present study examined the effects of food deprivation on neural progestin receptor binding using an in vitro binding assay and on progestin receptor immunoreactivity (PRIR) in estradiol-primed, OVX hamsters. Parallel behavior tests for sexual behavior were also performed in both experiments. OVX hamsters received 2.5 micrograms estradiol benzoate and were fed ad libitum or food deprived at the same time. Forty-eight hours later, animals were killed in preparation for the immunocytochemistry or progestin receptor assay. Binding assays indicated that 48-h food deprivation decreased progestin receptor levels in the preoptic area and had no effect in the mediobasal hypothalamus, an area that includes the VMH and the arcuate nucleus (ARH). Immunocytochemical analysis confirmed these findings. Food deprivation caused a decrease in sexual receptivity and in the number of detectable PRIR cells in the MPO and medial amygdala but had no effect on the number of detectable PRIR cells in the VMH/VLH, the ARH, or the anteroventral periventricular nucleus. These results suggest that food deprivation modulates progestin receptor binding and PRIR in a site-specific manner. In addition, the effects of food deprivation on neural ERIR and PRIR are significantly different.

Animals↗
PubMed1981

Progesterone receptors in the cerebral cortex of neonatal female rats.

Progestin-binding components were detected in cerebral cortical cytosols from female rats at 7 days of age. These components labeled in vitro with a tritiated synthetic progestin. R5020, sediment in the 7S region in sucrose density gradients containing 10% glycerol. The dissociation constants and the number of binding sites of the components were 3.9 X 10(-10)M and 47.5 fmol/mg cytosol protein, respectively, indicating high affinity and low capacity binding. The 7S-binding components were specific for progestational compounds. Estradiol competed weakly. Incubation with pronase abolished the 7S progestin binding. Heat experiments suggested a thermolabile nature of the components. These results suggest that the cytosols from the cerebral cortex of 7-day-old female rats contain progesterone receptors.

Animals↗
PubMed1980

A sex difference in the progestin receptor system of guinea pig brain.

Female guinea pigs are more sensitive than males to the lordosis-promoting effects of sequential estradiol-progesterone treatment. This study explored a possible cellular basis for this reduced sensitivity. Cytoplasmic progestin receptor concentrations were determined using a [3H]R5020 binding assay for a dissection of brain tissue which included the hypothalamus, preoptic area and septum (HPS) from male and female guinea pigs 40 h after administration of estradiol benzoate (EB). Male guinea pigs injected with 10 micrograms EB have a progestin binder in cytosol from HPS and cerebral cortex that is similar to that in females on the basis of apparent dissociation constant and steroid specificity. Injection of either 1.6 or 10 micrograms EB caused a larger increase in the concentration of cytoplasmic progestin binding in female HPS compared to the same dose in males. A 10 microgram EB injection induced a concentration of progestin binding in male hypothalamus not significantly different from that induced in female hypothalamus by a 1.6 microgram EB injection (a dose that consistently facilitates sexual recepivity in females when followed 40 h later by 0.5 mg progesterone). Despite the induction by EB of a behaviorally-sufficient concentration of cytoplasmic progestin receptors, fewer males (3/10) than females (8/10) responded to EB (10 micrograms)-progesterone treatment with the expression of lordosis. Finally, using a nuclear progestin receptor [3H]R5020 exchange assay, we found that male guinea pigs injected with 10 micrograms EB accumulated a slightly lower concentration of progestin receptors in HPS cell nuclei 4 h after a 0.5 mg progesterone injection than similarly-treated females. Therefore, male guinea pigs show decreased induction of cytoplasmic progestin receptors in HPS after estradiol injection, and a decreased cell nuclear accumulation of these receptors after progesterone injection compared to females. We conclude that this sex difference in the progestin receptor system is insufficient to account, in itself, for the sex difference in behavioral sensitivity to estradiol and progesterone.

Animals↗
PubMed1981

In situ estradiol and progestin (R5020) localization in the vascularly separated and isolated hypothalamus of the rhesus monkey.

A neurosurgical procedure has been developed for vascular isolation of the hypothalamus-thalamus region of the rhesus monkey brain. Utilizing this preparation, the left and right halves of the hypothalamus were perfused simultaneously, but separately, with a dextran-blood solution. Radiolabeled steroids were directly perfused in the dextran-blood into either the left or right half of the hypothalamus. Studies with radiolabeled gonadal steroids indicate that the majority of the carotid circulation is confined to the hypothalamus-thalamus area in this brain preparation and the cross-circulation of labelled steroids between the left and right sides of the hypothalamus is less than 10%. The usefulness of the preparation is illustrated by an autoradiographic study of the in situ hypothalamic distribution of (3H)estradiol in ovariectomized rhesus monkeys and of the synthetic progestin(3H)R5020 in estrogen-primed, ovariectomized rhesus monkeys. The direct perfusion of the (3H) steroids into the hypothalamus greatly increases the sensitivity of such compared to systemic administration of the (3H) steroids. The perfusion of one-half of the hypothalamus with )3H) steroid and the other half with (3H) steroids. The perfusion of one-half of the hypothalamus with (3H) steroid and the other half with (3H) steroids. The perfusion of one-half of the hypothalamus with (3H) steroid and the other half with (3H)steroid plus radioinert steroids permits in 1 animal, acting as its own control, the examination of a saturable distribution of a gonadal steroid in the rhesus monkey hypothalamus.

Animals↗
PubMed1984

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)

Animals↗
PubMed1984

Supplemental progesterone delays heat termination and the loss of progestin receptors from hypothalamic cell nuclei in female guinea pigs.

Previous studies indicate that the retention of hypothalamic nuclear progestin receptors parallels the expression of sexual receptivity in ovariectomized, hormonally treated guinea pigs. In this study, the effect of a supplemental progesterone injection on heat termination and retention of nuclear progestin receptors was examined. Ovariectomized guinea pigs were injected with 50 micrograms progesterone 48 h after receiving 4 micrograms estradiol benzoate and were tested hourly for lordosis. 8 h after progesterone treatment, animals received either 500 micrograms progesterone or the oil vehicle. The supplemental progesterone injection delayed the termination of heat by more than 2 h compared to oil-injected animals. The effect of supplemental progesterone on the retention of nuclear progestin receptors was then determined. Animals were killed 8, 10, or 14 h after the initial injection of progesterone, and cytosol and nuclear progestin receptor concentrations in mediobasal hypothalamus-preoptic area were determined. Supplemental progesterone further increased the level of nuclear progestin receptors measured at 10 h, and at 14 h these levels were still elevated above baseline. In contrast, nuclear progestin receptor levels in animals which received only the initial progesterone injection had returned to baseline by 14 h, a time when similarly treated animals were no longer receptive. These results suggest that the mechanism by which heat termination occurs may involve loss of nuclear progestin receptors.

Animals↗
PubMed1984

Criteria for the establishment of a double-labeling assay for simultaneous determination of estrogen and progesterone receptors.

The availability of [125I]-16 alpha-iodo-3,17 beta-estradiol ( [125I]-E2) with binding characteristics similar to estrogen receptor (ER) enabled us to establish a double-labeling assay for the simultaneous determination of ER and progesterone receptors (PgR) using 125I-E2 and [3H]-R5020. The criteria for the establishment of such a double-labeling assay are described. 150 human mammary tumor cytosols have been investigated with the standard routine receptor assay for ER as well as PgR and the results were compared to those obtained by the double-labeling assay. ER: a coefficient of correlation of 0.691 was obtained, the parameters of the regression line were Y = 1.025 X X-0.036. When referring to the standard assay, 3 determinations were false-positive and 4 false-negative. PgR: a correlation coefficient of 0.984 was found, the parameters of the regression line were Y = 0.960 X X + 12.16. One value was false-negative and 1 false-positive. An equivalence of the two methods could be demonstrated. This new assay reduces by half the amount of tissue necessary for a valid 4- to 6-point saturation analysis, the time required for performing the assay and its cost.

Binding, Competitive↗
PubMed1979

The endocrine background of human renal cell carcinoma. I. Binding of the highly potent progestin R 5020 by tumour cytosol.

Based on the potential sensitivity of the growth of human renal cell carcinoma, tumour tissue from 88 patients was analysed for progestin receptors. With the dextran-coated charcoal assay, cytoplasmic components which bound the potent progestin R 5020 specifically and with high affinity could be detected in 42% of the carcinomas. The apparent dissociation constant of the R-5020-binder complex amounted to 3.1 +/- 1.2 X 10(-8) mol/l. Sedimentation in sucrose gradients revealed the bulk of these components to be in the 4-S region. The ligand specificity for binding to these sites indicated a requirement for progestins. Despite the enormous case material investigated, we were unable to confirm the presence of the high receptor concentrations reported in the literature.

Adenocarcinoma↗
PubMed1979

The endocrine background of human renal cell carcinoma. II. Attempt to induce the R-5020-binding components by oestrogens.

In an attempt to elevate the concentration of progestin-binding components in human renal cell carcinoma, 24 patients were treated prior to tumour nephrectomy with various doses of oestrogens, potent inducers of progestin receptor synthesis. Low-dose oestrogen treatment was found to be insufficient to significantly induce progestin-binder synthesis in the tumour tissue. In the carcinoma of patients receiving high-dose oestrogen treatment, the average concentration of R-5020-binding sites did not differ from that of the low-dose group. However, 2 out of these patients (12.5%) exhibited R-5020-binder concentrations in the tumour tissue which exceeded the highest quantities of progestin-binding components found in 88 untreated controls previously analysed in our laboratory.

Adenocarcinoma↗
PubMed1979

The endocrine background of human renal cell carcinoma. III. Role of inhibitors of R 5020 binding in tumour cytosol.

Cytosol preparations obtained from 9 different human renal cell carcinomas were investigated for the eventual presence of progestin-binding inhibitors which might offer an explanation for the previous failure to demonstrate high receptor levels in the tumour tissue. The inhibitory potency of these preparations was estimated by measuring the decrease of R 5020 binding to uterine progestin receptors in the presence of tumour cytosol. Interestingly, cytosol from human renal cell carcinoma was found to contain progestin-binding inhibitors. The average inhibition of R-5020-receptor interaction amounted to 46%. In only 1 out of 9 cases, binding was completely suppressed. In order to circumvent the inhibitory reaction potentially occurring in cell-free systems, R-5020-binding studies additionally were performed in cell suspension. Out of 7 carcinomas studied using this assay system, 5 did not contain any specific progestin-binding entities. In 1 tumour, receptor-atypical non-saturable binding was observed. Only in isolated cells prepared from 1 other carcinoma, could slight indications for the presence of low concentrations of progestin receptors be detected.

Adenocarcinoma↗
PubMed1981

Binding of dihydrotestosterone, R 1881 and R 5020 in cytosols from normal, benign hypertrophic and cancerous human prostates.

The binding of dihydrotestosterone, R 1881 and R 5020 was examined in cytosols of normal, benign hypertrophic and cancerous tissues of the human prostates. Almost all samples obtained by open operation showed high affinity binding to these ligands. Dissociation constants of the binding to these ligands were approximately 10(-9) M irrespective of the pathological state of the prostates. Maximum binding sites for dihydrotestosterone seemed to be greater in normal tissues than in the pathological ones. However, maximum binding sites for R 1881 and R 5020 were not significantly different among the normal and pathological prostates examined in the present study. Moreover, some correlation was observed between the maximum binding sites for R 1881 and those for R 5020. The samples resected by TUR seemed to be inadequate for analyses of androgen binding.

Cytosol↗
PubMed1986

Determination of androgen receptors in human benign prostatic hypertrophy with two synthetic radiolabeled ligands.

Nuclear and cytosolic androgen receptor concentrations in tissues of human benign prostatic hypertrophy (BPH) were determined by use of methyltrienolone (R-1881) and 7 alpha,17 alpha-dimethyl-19-nortestosterone (DMNT) as radiolabeled ligands. Cytosolic R-1881-binding sites were 46.1 +/- 43 fmol/mg protein and nuclear R-1881-binding sites were 51.8 +/- 42 fmol/mg protein. DMNT-binding sites in cytosol were 44.3 +/- 38 fmol/mg protein and in nuclear extract 73.4 +/- 64 fmol/mg protein. No significant correlation was found between the number of R-1881- and DMNT-binding sites in either cytosol or nuclear extracts. Cytosolic or nuclear androgen receptor content was not significantly correlated with the percentage of epithelial or stromal cells as determined from the corresponding histological sections. In BPH tissue with marked cystic degeneration, very low androgen receptor levels were found.

Cell Nucleus↗
PubMed1987

Characterization of the nuclear progesterone receptor in normal human endometrium after progesterone injection.

Nuclear progesterone receptors (RPN) were characterized in the 0.4 M KCl nuclear extract of the endometrium using [3H]R5020 as a ligand, in women in the proliferative phase of the cycle (n = 5), in the midcycle (n = 5), in the secretory phase (n = 4), and in premarin-treated women (n = 3), 1-3 h following progesterone injection. The receptor character of the binding was demonstrated by high specificity for progestin binding, high saturable affinity for R5020 and a sedimentation constant of about 3S in sucrose density gradient. The RPN characteristics were similar in all 4 groups and were also similar to those of the remaining cytosolic RP. Despite the fact that total RP levels differed in all 4 groups, the percentage of the receptor that was measured in the nuclear extract was similar in all groups and ranged from 52 to 61% of the total RP levels.

Adult↗
PubMed1982

Are the histological and ultrastructural features of endometrial carcinomas reliable indicators of their steroid receptor content?

The histological and ultrastructural features of 15 endometrial carcinomas were analyzed and recorded without knowledge of the steroid receptor content which was determined in the cytosol of the tumor tissue. Serum levels of estrogens were determined in all patients. The importance of this simultaneous determination of the levels of circulating steroid hormones is emphasized. Some degree of correlation was found between the histological grading of the neoplasms and their steroid receptor content. On the contrary, no evident relation seems to exist between steroid hormone-binding capacity and ultrastructural features of the tumor cells. These different results are presented and discussed.

Aged↗
PubMed1982

Hormone receptors of the baboon cardiovascular system. Biochemical characterization of aortic and myocardial cytoplasmic progesterone receptors.

We used the synthetic progestin R5020 (17 alpha, 21-dimethyl-19-norpregna-4,9-diene-3,20-dione) to characterize cytoplasmic progesterone receptors in baboon (Papio sp.) aorta and myocardium. The relative ability of selected steroids to inhibit binding of radiolabeled R5020 to aortic cytoplasmic progesterone receptors was radioinert R5020, 1.0; progesterone, 0.31; triamcinolone acetonide, 0.06; testosterone, 0.002; estradiol-17 beta, 0.01; and cortisol. 0.001. The relative ability of these same steroids to inhibit binding of radiolabeled R5020 to myocardial cytoplasmic progesterone receptors was, respectively, 1.0, 0.58, 0.21, 0.01, 0.01, and 0.001. Both aortic and myocardial cytoplasmic progesterone receptors migrated as macromolecules with a sedimentation coefficient of 8-9S on low ionic strength linear sucrose gradients. Cytoplasmic binding of R5020 was inactivated by incubation of 37 degrees C. Saturation analysis at 2 degrees C showed aorta and myocardium, respectively, contained 41.6 +/- 16.1 (mean +/- SD) and was 14.0 +/- 2.8 fmol R5020 binding sites/mg cytosol protein. The dissociation constant for R5020 was 2.8 +/- 1.2 nM, aorta, and 2.0 +/- 1.1 nM, myocardium. The presence of progesterone receptors in baboon cardiovascular tissues suggests that progestins may directly influence cardiovascular tissue function.

Animals↗
PubMed1984

Antiestrogenic action of dihydrotestosterone in mouse breast. Competition with estradiol for binding to the estrogen receptor.

Feminization in men occurs when the effective ratio of androgen to estrogen is lowered. Since sufficient estrogen is produced in normal men to induce breast enlargement in the absence of adequate amounts of circulating androgens, it has been generally assumed that androgens exert an antiestrogenic action to prevent feminization in normal men. We examined the mechanisms of this effect of androgens in the mouse breast. Administration of estradiol via silastic implants to castrated virgin CBA/J female mice results in a doubling in dry weight and DNA content of the breast. The effect of estradiol can be inhibited by implantation of 17 beta-hydroxy-5 alpha-androstan-3-one (dihydrotestosterone), whereas dihydrotestosterone alone had no effect on breast growth. Estradiol administration also enhances the level of progesterone receptor in mouse breast. Within 4 d of castration, the progesterone receptor virtually disappears and estradiol treatment causes a twofold increase above the level in intact animals. Dihydrotestosterone does not compete for binding to the progesterone receptor, but it does inhibit estrogen-mediated increases of progesterone receptor content of breast tissue cytosol from both control mice and mice with X-linked testicular feminization (tfm)/Y. Since tfm/Y mice lack a functional androgen receptor, we conclude that this antiestrogenic action of androgen is not mediated by the androgen receptor. Dihydrotestosterone competes with estradiol for binding to the cytosolic estrogen receptor of mouse breast, whereas 17 beta-hydroxy-5 beta-androstan-3-one (5 beta-dihydrotestosterone) neither competes for binding nor inhibits estradiol-mediated induction of the progesterone receptor. Dihydrotestosterone also promotes the translocation of estrogen receptor from cytoplasm to nucleus; the ratio of cytoplasmic-to-nuclear receptor changes from 3:1 in the castrate to 1:2 in dihydrotestosterone-treated mice. Thus, the antiestrogenic effect of androgen in mouse breast may be the result of effects of dihydrotestosterone on the estrogen receptor. If so, dihydrotestosterone performs one of its major actions independent of the androgen receptor.

Animals↗