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Biomedical subjects

H Coirini

Publications and source records attributed to H Coirini.

At least 37 records · Page 2Linked to original sources
PubMed1991

Regulation by dopaminergic neurotransmission of dopamine D2 mRNA and receptor levels in the striatum and nucleus accumbens of the rat.

The effect of dopamine depletion or pharmacological blockade of dopamine receptors on striatal and accumbens dopamine D2 mRNA and receptor levels was assessed by in situ hybridization histochemistry and receptor autoradiography. The time course of pharmacological blockade with haloperidol demonstrates a complex mode of regulation of dopamine D2 mRNA and receptor levels. By day 8 of haloperidol treatment, D2 mRNA and receptor levels were decreased (up to 20%) in the medial and anterior aspects of the caudate-putamen (mCPU and aCPU) and the nucleus accumbens (NAc). However, by day 21 of haloperidol treatment, D2 mRNA and receptor were increased relative to vehicle-injected controls. Likewise, unilateral dopamine depletion due to 6-hydroxydopamine (6-OHDA) lesions of mesencephalic dopaminergic neurons resulted in decreased levels of D2 receptor mRNA by day 8 post-lesion in the ipsilateral mCPU, aCPU and the NAc. However, at days 14 or 21 post-lesion, there was a reversal of the effect with increases of up to 22% in all brain regions ipsilateral to the lesion. Although no decreases in receptor level were observed at day 8, significant increases in receptor level in all three brain regions were detected at days 14 and 21 post-lesion. The results demonstrate that midbrain dopaminergic innervation exerts tonic effects on the levels of dopamine D2 receptor and mRNA in the caudate-putamen and the nucleus accumbens of the rat. Changes in receptor level are frequently accompanied by comparable changes in mRNA level, indicating a mass action relationship between receptor level and receptor biosynthesis in these forebrain regions in the rat.

Animals↗
PubMed1991

Steroid hormones as mediators of neural plasticity.

Steroid and thyroid hormone receptors are expressed in the developing brain and persist throughout adult life. They mediate a variety of effects on the brain, ranging from developmental effects of thyroid hormone and the process of sexual differentiation to the cyclic changes during reproductive cycles in adult female animals. This review summarizes data from the author's laboratory on three topics: (1) actions of extradiol and progesterone on the ventromedial nucleus of the hypothalamus in adult female and male rats, showing both the cyclicity and the consequences of brain sexual differentiation; (2) actions of estradiol on the cholinergic neurons of the basal forebrain of the female and male rat, reflecting the plasticity of the adult cholinergic system as well as sex differences which are developmentally programmed; and (3) diverse actions of estrogens, thyroid hormone and glucocorticoids on the morphology of hippocampal neurons. The review concludes by discussing the interactions between "organizational" (i.e. developmental) effects and the "activational" effects of steroids on the mature nervous system in relation to the environmental control of brain gene expression.

Animals↗
PubMed1991

Light-dark differences in behavioral sensitivity to oxytocin.

Ovariectomized female rats treated with estradiol benzoate (EB) and progesterone (P) were infused intracerebroventricularly with a low (200 ng) or high (1 microgram) dose of oxytocin (OT). The low dose of OT facilitated lordosis behavior only during the dark phase of the light-dark cycle in females that were pretreated with low doses of EB (2 micrograms) and P (250 micrograms). In contrast, the high dose of OT facilitated lordosis behavior during both the light and the dark phases but only in long-term ovariectomized females that were primed with large amounts of EB (2 x 10 micrograms) and P (500 micrograms). In females that were primed with lower amounts of ovarian steroids, the high dose of OT failed to increase levels of lordosis responding in either the dark or light phase. Thus, when female rats are treated with physiological amounts of ovarian hormones and OT, they are more sensitive to the facilitative effects of the OT on lordosis behavior during the dark phase.

Animals↗
PubMed1991

The regulation of oxytocin receptor binding in the ventromedial hypothalamic nucleus by testosterone and its metabolites.

Oxytocin (OT) receptor binding in the ventromedial hypothalamic nucleus is regulated by testosterone (T) in male rats. However, T is metabolized in the brain, and many of the central effects of T are mediated by its metabolites. The experiments reported here were designed to determine whether T affects OT receptor binding directly or through the action of its metabolites 17 beta-estradiol and 5 alpha-dihydrotestosterone. Adult male rats were either sham operated or castrated and treated 1 week later with T propionate (TP), 17 beta-estradiol benzoate (EB), dihydrotestosterone benzoate (DHTB), DHTB plus EB, or oil. OT receptor binding was assessed autoradiographically using [125I]d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT. In addition, seminal vesicle weights were measured as an index of androgenic activity. These experiments showed that TP and DHTB plus EB increased OT receptor binding in the ventromedial hypothalamic nucleus to the levels in intact males. Treatment with EB alone partially reinstated binding to the levels in intact males, while DHTB treatment was without effect. Castrated males treated with either TP or DHTB had seminal vesicle weights comparable to those of gonadally intact males and greater than those of animals in all other steroid conditions, indicating that sufficient levels of circulating steroids were attained in these groups. These data suggest that the induction of hypothalamic OT receptor binding by T is the result of the combined actions of estradiol and dihydrotestosterone. However, the mechanism underlying this interaction is unknown.

Animals↗
PubMed1991

Transport of estrogen-induced oxytocin receptors in the ventromedial hypothalamus.

The modulation of oxytocin (OT) receptors (OTRs) by estrogen was investigated in the ventromedial hypothalamus by in vitro receptor autoradiography. Treatment of ovariectomized and adrenalectomized rats with various doses of estradiol benzoate (EB) increased OTR binding not only in the ventromedial nuclei of the hypothalamus (VMN), but also in the area lateral to the nuclei (IVMN). After a single injection of EB, OTRs first were induced within the ventrolateral parts of the VMN, and only hours later they appeared in the IVMN. This is consistent with the interpretation that OTRs are first induced within the estrogen-sensitive neurons of the ventrolateral VMN and then are transported laterally out of the nuclei. Two additional experiments confirmed this interpretation. First, local infusion of a low dose (10 micrograms) of the neuronal transport inhibitor vinblastine blocked the appearance of OTRs in the IVMN but did not prevent the induction of OTRs by EB within the nuclei. Second, a knife cut placed lateral to the VMN prevented the spread of OTRs out of the nuclei. However, even after treatment with a high dose of EB (2 x 10 micrograms), progesterone (P) was required for a maximal extension of the area covered by OTRs. Thus, the OTR is an estrogen-induced neurotransmitter receptor that is transported to its site of action, the lateral ventromedial hypothalamus, where it is modulated by P and where estrogen-induced OT immunoreactivity is found.

Animals↗
PubMed1990

Behavioral effects of progesterone associated with rapid modulation of oxytocin receptors.

The ventromedial nuclei of the hypothalamus (VMN) are important for the control of feminine mating behavior, and hormone action within these nuclei has been causally related to behavior. Estradiol induces receptors for oxytocin in the VMN and in the area lateral to these nuclei over the course of 1 to 2 days, and progesterone causes, within 30 minutes of its application, a further increase in receptor binding and an expansion of the area covered by these receptors lateral to the VMN. The rapid progesterone effect appears to be a direct and specific effect of this steroid on the receptor or membrane, because it was produced in vitro as well as in vivo and was not mimicked by a variety of other steroids. The effect of progesterone occurred in the posterior part of the VMN, where oxytocin infusion facilitated feminine mating behavior; it did not take place in the anterior part of the VMN, where oxytocin infusion had no effect on mating behavior.

Animals↗
PubMed1990

Steroid effects on neuronal activity: when is the genome involved?

For over four decades steroids have been regarded first as facilitators of enzymic reactions and subsequently as activators of genomic activity. The brain, long studied in terms of its bioelectric properties and anatomical connectivity, has now been recognized as a complex target tissue for genomic effects of steroid hormones, which bring about long-lasting alterations in brain structure and neurochemistry as well as changes in behaviour and neuroendocrine function. Studies of steroid effects on brain bioelectric activity have also shown rapid effects which are difficult to explain by a strictly genomic mechanism. One way to distinguish between genomic and non-genomic effects is by the time course, with extremely rapid effects being non-genomic and delayed effects being genomic. Effects with onset latencies of minutes to an hour may be due to either mechanism. Examples illustrating genomic actions include delayed effects of oestrogen which alter oxytocin and GABAA receptors and induce spines on dendrites and delayed glucocorticoid effects on neuronal survival. There are also examples of apparent genomic effects of oestradiol which interact with rapid and apparently non-genomic effects of progesterone: progesterone rapidly promotes spread of oestrogen-induced oxytocin receptors in ventromedial hypothalamus and rapidly modifies oestrogen-regulated GABAA receptor density in hypothalamus. The former effect is one produced by progesterone itself whereas the latter effect may be related to the ability of progesterone metabolites to interact with the chloride channel of the GABAA-benzodiazepine receptor complex.

Animals↗
PubMed1989

Changes of salt intake and of (Na+K)-ATPase activity in brain after high dose treatment with deoxycorticosterone.

Mineralocorticoids (MC) have a dual effect on salt intake: in adrenalectomized rats, they reduce previously elevated salt intake; and in intact rats a high MC dose increases salt intake. We have studied the activity of (Na+K)-ATPase and [3H]ouabain binding in rats treated with deoxycorticosterone (DOC) in doses that elicited a salt appetite. Brains were removed from control and treated animals, and 20 different areas were punched out from brain slices cut every 300 microns. DOC treatment significantly reduced (Na+K)-ATPase activity in the lateral hypothalamic area, anterior amygdaloid and lateral amygdaloid nuclei, while increasing it in the periventricular gray matter; changes in other regions were not significant. Binding of [3H]ouabain was not modified by DOC treatment. In parallel experiments, we determined MC receptors in adrenalectomized rats. Binding of [3H]aldosterone was preferentially found in hippocampus, followed by lateral septum, anterior, posterior and lateral amygdaloid areas, with lower levels in other regions. However, there was no correlation between [3H]aldosterone binding and (Na+K)-ATPase activity in brain punches from either control or DOC-treated rats. Further experiments are needed to ascertain if (Na+K)-ATPase changes in discrete areas of the brain containing moderate levels of mineralocorticoid receptors, are related to the behavioral effects of DOC.

Animals↗
PubMed1989

Regulation of high-affinity GABAA receptors in the dorsal hippocampus by estradiol and progesterone.

The effects of estradiol benzoate (EB) and of progesterone (P) treatment on high-affinity [3H]muscimol binding in the dorsal hippocampal formation were examined in ovariectomized and adrenalectomized female rats by in vitro autoradiography. EB injected subcutaneously increased [3H]muscimol binding in specific subregions of the Ammon's horn (CA1 and stratum radiatum of CA4) and of the dentate gyrus (dorsal molecular layer). In these particular regions, estrogen receptors have been shown to be present. P did not significantly affect [3H]muscimol binding in any region of the hippocampus when administered alone or in combination with EB. Results suggest that estrogens may regulate the activity of specific hippocampal neurons by modulating their sensitivity to GABA.

Adrenalectomy↗
PubMed1989

Localized actions of progesterone in hypothalamus involve oxytocin.

Two ovarian hormones, estradiol and progesterone, which facilitate mating behavior in the female rat by acting on the ventromedial nuclei (VMN) of the hypothalamus, induce changes in oxytocin receptor binding in this brain region. Estradiol induced a 4-fold increase in the oxytocin receptor binding of the VMN and surrounding area and increased the number and immunostaining of oxytocin fibers in an area lateral to the ventral VMN. Progesterone, in estrogen-primed rats, caused the induced oxytocin receptors to spread over the area containing the oxytocin fibers. Infusion of oxytocin into the ventromedial hypothalamus increased the display of lordosis behavior only in females primed with both estradiol benzoate and progesterone. Thus, the sequential actions of two ovarian hormones bring a neuropeptide and its receptors into register and enable the neuropeptide to exert behavioral effects.

Adrenalectomy↗
PubMed1989

Estradiol modulation of oxytocin binding in the ventromedial hypothalamic nucleus of male and female rats.

It has been suggested that estradiol and oxytocin (OT) may interact as neuroendocrine components in the regulation of sexual behavior. In the present study the effect of estradiol benzoate (EB) treatment (50 micrograms/kg body weight/2 days) on [3H]-OT binding was evaluated in adult and 21-day-old gonadectomized male and female rat brains. Coronal sections through the ventro-medial nucleus of the hypothalamus (VMN) were analyzed in three different section planes. EB priming induced an increase in [3H]-OT binding in the VMN of both male and female rats. Greater binding site density and significant EB effects were found in the most caudal plane where the ventrolateral portion of the VMN is well defined at both ages. OT binding in the central amygdaloid nucleus was not affected by this treatment but higher binding levels were found in the most caudal sections irrespective of hormonal status or sex. No sex differences were detected in OT binding in the VMN of basal or EB-treated animals. These results suggest that a dose of EB which activates female sexual behavior in female but not in male rats is able to induce similar levels of OT binding in the VMN of animals of both sexes.

Aging↗
PubMed1989

Testosterone modulates oxytocin binding in the hypothalamus of castrated male rats.

Oxytocin (OT) binding sites are modulated by estrogens in several brain regions including the ventromedial hypothalamic nucleus (VMN) in both male and female rats. To further study steroid regulation of OT receptor binding, we examined the effect of androgen replacement in castrated male rats on OT binding with quantitative autoradiographic methods. Castrated adult male rats were treated with either 250 micrograms testosterone propionate (TP) or oil for 2 days and killed 48 h after the last injection. Brain sections through the preoptic area and VMN were labeled with 5.0 nM[3H]-OT +/- 5.0 microM unlabeled OT or 1.0 microM[Thr4,Gly7]OT and apposed to tritium-sensitive film for 7 weeks. Results of this study show that TP increased [3H]-OT binding up to 5-fold in the ventrolateral VMN and 4-fold in the bed nucleus of the stria terminalis. In addition [Thr4,Gly7]OT completely displaced [3H]-OT binding in the VMN indicating that binding in this brain region was specific to OT receptors. Because estrogens also increase OT receptor binding in male rats, it is possible that TP affects OT binding after being converted by aromatase to estradiol.

Animals↗
PubMed1989

Regulation of high-affinity GABAa receptors in specific brain regions by ovarian hormones.

The regulation of 3H-muscimol binding to high-affinity GABAa receptors by estradiol (E) and by progesterone (P) was studied within discrete brain regions using in vitro quantitative autoradiography. Treatment of ovariectomized and adrenalectomized female rats with E resulted in a decrease of muscimol binding only in specific estrogen-sensitive brain regions like the ventromedial nuclei (VMN) of the hypothalamus, the arcuate nucleus (ARC), the medial amygdala and the midbrain central grey (MCG). When administered alone, P had no effect. However, in estrogen-primed females, P increased muscimol binding in both VMN and MCG to levels seen in control animals. Thus, E and P exert opposite effects on the GABAa receptor within these two nuclei. As both hormones facilitate female reproductive behavior as well as the release of luteinizing hormone, present results suggest that E and P affect muscimol binding by different mechanisms.

Adrenalectomy↗
PubMed1989

Anatomical localization of the effects of 17 beta-estradiol on oxytocin receptor binding in the ventromedial hypothalamic nucleus.

Oxytocin (OT) neurotransmission plays a role in the facilitation of steroid-dependent sexual receptivity in the rat. One way in which the ovarian steroid 17 beta-estradiol (E2) has been shown to modulate OT transmission is by increasing OT receptor binding in certain brain areas involved in the regulation of female sexual behavior such as the ventromedial hypothalamic nucleus (VMN). This study was undertaken to describe the distribution of OT receptors within the VMN that are regulated by physiological levels of E2. With quantitative autoradiographic methods, we measured [3H]OT binding in ovariectomized female rats implanted with Silastic capsules containing cholesterol, 5% E2, or 100% E2. In addition, plasma E2 levels, pituitary progestin receptor binding, and uterine weights were measured in animals from each treatment group. Results of this study showed that physiological levels of E2 increased [3H]OT binding in caudal regions of the ventrolateral VMN and stimulated maximal uterine growth and pituitary progestin receptor binding. However, in more rostral VMN sections, E2 induced a dose-dependent increase in [3H]OT binding. These data suggest that ovarian steroids sensitize the brain to OT by increasing OT receptor binding in certain brain areas involved in the regulation of sexual receptivity.

Animals↗
PubMed1989

Time course of the estradiol-dependent induction of oxytocin receptor binding in the ventromedial hypothalamic nucleus of the rat.

Oxytocin (OT) transmission is involved in the steroid-dependent display of sexual receptivity in rats. One of the biochemical processes stimulated by the ovarian steroid 17 beta-estradiol (E2) that is relevant to reproduction is the induction of OT receptor binding in the ventromedial hypothalamic nucleus (VMN). The purpose of these experiments was to determine if E2-induced changes in OT receptor binding in the VMN occur within a time frame relevant to cyclic changes in ovarian steroid secretion. OT receptor binding was measured in the VMN of ovariectomized rats implanted for 0-96 h with E2-containing Silastic capsules. The rate of decay of OT receptor binding was measured in another group of animals 6-48 h after capsule removal. Receptors were labeled with the specific OT receptor antagonist [125I]d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH2(9)]OVT, and binding was measured with quantitative autoradiographic methods. In addition, plasma E2 levels and uterine weights were assessed in animals from each treatment condition. Significant increases in E2-dependent OT receptor binding and uterine weight occurred within 24 h of steroid treatment. After E2 withdrawal, OT receptor binding and uterine weight decreased significantly within 24 h. These results are consistent with the hypothesis that steroid modulation of OT receptor binding is necessary for the induction of sexual receptivity.

Animals↗
PubMed1988

Steroid modulation of the chloride ionophore in rat brain: structure-activity requirements, regional dependence and mechanism of action.

Further in vitro studies of steroids active at the gamma-aminobutyric acidA (GABAA) receptor regulated Cl- channel labeled by [35S]-t-butylbicyclophosphorothionate ([35S]TBPS) reveal additional structural requirements necessary for activity. Evaluation of selected steroids for activity against TBPS-induced convulsions show similar requirements for activity. Interestingly, steroids (e.g., 5 alpha-pregnan-3 alpha, 20 alpha-diol) were identified that have high potency but limited efficacy as modulators of [35S]TBPS binding. These characteristics are reminiscent of the clinically useful benzodiazepines (BZs) such as clonazepam. However, interactions between the prototypical anesthetic-barbiturate, sodium pentobarbital, and steroids active at the Cl- channel suggest that they do not share a common site of action as allosteric modulators of [35S]TBPS and BZ receptor binding. The most potent steroid evaluated, 5 alpha-pregnan-3 alpha-ol-20-one, modulates [35S]TBPS binding at low concentrations (IC50 approximately 17 nM) in a regionally dependent manner. All [35S]TBPS binding sites appear to be functionally coupled to a steroid "modulatory site." Because several of the active steroids are metabolites of progesterone, their ability to inhibit the binding of [3H]promegestrone to the cytosolic progestin receptor in rat uterus was evaluated. Those steroids showing potent activity at the GABAA receptor-Cl- ionophore were inactive at the intracellular progestin receptor. Such specificity coupled with their high potency provide additional support for the hypothesis that some of these steroids may be involved in the homeostatic regulation of brain excitability via the GABAA-BZ receptor complex.

Androstane-3,17-diol↗