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J D Blaustein

Publications and source records attributed to J D Blaustein.

At least 109 records · Page 6Linked to original sources
PubMed1984

1-(o-Chlorophenyl)-1 (p-chlorophenyl)2,2,2-trichloroethane induces functional progestin receptors in the rat hypothalamus and pituitary gland.

A recent report suggests that estrogen induction of hypothalamic progestin receptors is not a prerequisite for the facilitation by progesterone of female sexual behavior in rats. Progesterone was found to facilitate sexual behavior despite no apparent induction of progestin receptors by 1-(o-chlorophenyl) 1-(p-chlorophenyl)2,2,2-trichloroethane (o,p'-DDT). To investigate these findings further, ovariectomized rats were treated with daily injections of o,p'-DDT for 3 days, followed by progesterone on day 4. Daily injections of 400 mg o,p'-DDT/kg resulted in activation of lordosis in 50% of the animals; injections of 200 mg/kg were ineffective. Cytoplasmic and nuclear progestin receptor levels in the mediobasal hypothalamus-preoptic area and pituitary gland were then determined in similarly treated animals. Because competition assays revealed that o,p'DDT interacts with progestin-binding sites in vitro, residual o,p'-DDT was removed from the cytosol fraction before assay. o,p'-DDT treatment increased the level of cytoplasmic progestin receptors by 43% compared with that in oil-injected controls. Progesterone administration to DDT-treated rats resulted in a 137% increase in the level of nuclear progestin receptors relative to levels observed in animals receiving no progesterone. These findings contradict a previous report using o,p'-DDT and support the hypothesis that estrogen-induced progestin receptors are required for the facilitation of sexual receptivity by progesterone.

Animals↗
PubMed1982

A decrease of cytosol estrogen receptors in the hypothalamus as a result of treatment of neonatal rats with glutamate.

Experiments were performed to determine whether the neuroendocrine dysfunctions of rats treated neonatally with monosodium glutamate (MSG) could be related to a loss of cytoplasmic estrogen receptors. Female rats treated with MSG as neonates were ovariectomized as adults and killed by decapitation 2 or 3 weeks after ovariectomy. Body, gonadal and anterior pituitary gland weights in MSG-treated rats were depressed when compared to that seen in their littermate controls. Serum prolactin concentration was elevated in the MSG-treated rats. Serum luteinizing hormone (LH) concentration was significantly lower in MSG-treated rats than in controls at 2 weeks, but not at 3 weeks after ovariectomy, suggesting a sluggish postovariectomy rise of serum LH concentration. Serum follicle-stimulating hormone (FSH) concentration was not altered by the MSG treatment. The concentration of cytosol estrogen receptors in the anterior pituitary gland was similar to that of controls, but hypothalamic concentration of estrogen receptors decreased as a result of the MSG treatment. After dissection of different hypothalamic regions, it was found that the greatest depletion of the cytosol estrogen receptors occurred in the arcuate-median eminence region. The results raise the possibility that some reproductive impairments of MSG-treated rats could stem from a decrease in cytosol estrogen receptors in the arcuate-median eminence region.

Animals↗
PubMed1982

Failure of protein synthesis inhibition to block progesterone desensitization of lordosis in female rats.

Progesterone's desensitization effect on lordosis has been shown to correlate with a decreased concentration of hypothalamic progestin receptors after progesterone injection. In a recent study, one group of investigators found that the protein synthesis inhibitor anisomycin appeared to block progesterone's desensitization effect. Despite decreased levels of cytoplasmic progestin receptors, progesterone + anisomycin-treated rats exhibited a high level of lordosis four hr after a second progesterone injection. Because this finding conflicts with a progestin receptor model of progesterone's desensitization effect, we investigated it further. In the first experiments, ovariectomized rats were injected with estradiol benzoate followed 24 hr later by either progesterone or vehicle. Anisomycin injected 3 hr after progesterone, at a dose that causes inhibition of hypothalamic protein synthesis for at least 4 hr, was without effect on progesterone desensitization a day later. In other experiments silastic implants containing estradiol were inserted into ovariectomized rats. Forty-five hr later, rats received progesterone or vehicle, followed by injections of anisomycin or saline. Rats receiving anisomycin + progesterone were still highly receptive at 30 hr while saline + progesterone controls were not. Furthermore, the results were similar 4 hr after a second injection of progesterone at 30 hr. In a related experiment, we confirmed that anisomycin delayed dramatically termination of the period of sexual receptivity. In this laboratory anisomycin does not seem to block progesterone's desensitization effect. However, with certain procedures anisomycin delays the termination of sexual receptivity. Thus it is important in investigations of the mechanism of progesterone's desensitization effect that animals be tested prior to the second progesterone injection to determine if they are actually responding to the progesterone.

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↗
PubMed1980

Hormones modulate the concentration of cytoplasmic progestin receptors in the brain of male ring doves (Streptopelia risoria).

A cytoplasmic progestin receptor has been characterized in the brain of castrated ring doves using an in-vitro assay that measures the binding of a synthetic progestin, [3H]17 alpha,21-dimethyl-19-nor-pregna-4,9-diene-3,20-dione(promegestone; R5020). The affinity of the receptor was similar in both the hyperstriatum and the hypothalamus (Kd approximately equal to 4 X 10(-10) mol/l). Its concentration was higher in the anterior hypothalamus-preoptic area (63 +/- 4 fmol/mg (S.E.M.) protein) than in other brain regions (posterior hypothalamus, 33 +/- 5; hyperstriatum, 28 +/- 3; midbrain, 17 +/- 4 fmol/mg protein; n = 7). Progesterone and R5020 competed well for binding but oestradiol and 5 beta-dihydrotestosterone did not. Corticosterone and, to a lesser extent, testosterone and 5 alpha-dihydrotestosterone completed for binding but much higher concentrations were required than for progestins. Injections of testosterone (200 micrograms testosterone propionate daily for 7 days) significantly increased the concentration of progestin receptors in the anterior and posterior hypothalamus without having any significant effect on other brain areas. Shorter treatment, lasting for 2 days, with testosterone propionate (200 micrograms daily), 5 alpha-dihydrotestosterone (200 micrograms daily) or oestradiol benzoate (50 micrograms daily) did not always cause this increase but seven injections of oestradiol benzoate (50 micrograms daily for 7 days) were even more effective than seven injections of testosterone propionate (200 micrograms daily for 7 days). These data suggested that the sensitivity to progesterone of the brain of the bird changes as a consequence of increases in the level of testosterone in the circulation.

Animals↗
PubMed1979

Cytoplasmic progestin-receptors in guinea pig brain: characteristics and relationship to the induction of sexual behavior.

The synthetic progestin, R 5020, was used to measure cytoplasmic progestin receptors in the brain and pituitary gland of ovariectomized guinea pigs. Progestin receptors with a dissociation constant of 0.1--0.3 nM were measured by gel filtration in all brain regions studied, pituitary gland and the uterus. The receptor is progestin-specific; biologically potent progestins compete well against [3H]R 5020 for binding, but androgens, glucocorticoids and estrogens do not. The concentration of the cytoplasmic progestin receptor in hypothalamus-preoptic area-septum and midbrain is decreased in vivo by behaviorally effective doses of progesterone. In the pituitary gland, hypothalamus, preoptic area-septum and midbrain, but not other brain regions, the concentration of progestin receptors increases after estradiol benzoate-priming. The increase in the concentration of cytoplasmic progestin receptors in hypothalamus-preoptic area-septum is dependent on the dose of estradiol benzoate injected. After a single injection of a dose of estradiol benzoate routinely used to facilitate the display of sexual receptivity (1.6 microgram estradiol benzoate/animal), the latency to an increase and subsequent decrease in cytoplasmic progestin receptors in the hypothalamus-preoptic area-septum correlates well with the previously reported time course for progesterone's facilitation of sexual receptivity after estradiol benzoate injection. The experiments are consistent with the notion that brain progestin receptors mediate at least some of the behavioral effects of progesterone.

20-alpha-Dihydroprogesterone↗
PubMed1979

Inhibition of estrous behavior by progesterone in rats: role of neural estrogen and progestin receptors.

Sexual receptivity can be induced in ovariectomized rats with sequential injections of 17 beta-estradiol-3-benzoate (EB; 2 micrograms sc) and progesterone given 24 h apart. If a high dose of progesterone is used, estrous behavior is followed by a period during which sexual receptivity cannot be reinduced with a second progesterone injection (sequential inhibition). We have examined the effects of a hormone treatment which causes a sequential inhibition on levels of estrogen and progestin receptors in the hypothalamus-preoptic area-septum of ovariectomized rats. In a preliminary experiment, a single injection of 2 micrograms EB caused a significant increase in the concentration of brain cell nuclear estrogen receptors, Peak levels were seen at 12-24 h and remained significantly elevated as long as 72 h after EB. In a second experiment, we found that 48 h after EB, brain cytoplasmic estrogen receptors were significantly depressed and nuclear estrogen receptors were significantly elevated. However, a single progesterone injection (5 mg, sc) 24 h after EB had no significant effect on either cytoplasmic or nuclear estrogen receptor levels. Forty-eight hours after EB, brain cytoplasmic progestin receptors were significantly elevated compared with oil-injected controls. In a third experiment, progesterone (5 mg, sc) given 24 h after EB reduced neural cytoplasmic progestin receptors to levels significantly below those of oil-injected controls at 48 h. These results are consistent with the suggestion that progesterone does not interact with neural estrogen receptors to inhibit lordosis in rats. Rather, we suggest that progesterone may induce a behavioral refractoriness to subsequent progesterone treatments, at least in part, by reducing the concentration of neural cytoplasmic progestin receptors.

Animals↗
PubMed1977

Binding of [3H]estradiol by brain cell nuclei and female rat sexual behavior: inhibition by experimental diabetes.

In streptozotocin-diabetic female rats acute (24 h) withdrawal of insulin significantly impairs both estradiol + progesterone-induced sexual receptivity and cell nuclear concentration of [3H]estradiol in hypothalamus, preoptic area, and pituitary gland. Omission of insulin treatment for the first 24 h of a 30-h or 54-h estradiol benzoate-conditioning period significantly reduced mean lordosis ratings of ovariectomized-diabetic rats. Insulin withdrawal at the time of progesterone treatment and behavioral testing did not diminish sexual receptivity. One-half or 2 h after an intravenous injection of [3H]estradiol-17beta diabetic rats without insulin exhibited reduced cell nuclear [3H]estradiol concentrations (2 h) and/or diminished cell nuclear/whole homogenate concentration ratios (0.5 and 2 h). Twenty-four hour insulin withdrawal affected neither whole tissue [3H]estradiol uptake nor hypothalamus-preoptic area cytoplasmic estrogen-receptor content. These results: (1) suggest that diminished estradiol binding by target tissue cell nuclei may contribute to the well-known reproductive failures of female diabetics, and (2) support the concept that estradiol acts at the level of brain cell nuclei to induce female sexual behavior.

Animals↗