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Biomedical subjects

C Libertun

Publications and source records attributed to C Libertun.

At least 73 records · Page 4Linked to original sources
PubMed1986

Hormonal effects on unoccupied estrogen receptors in nuclei of anterior pituitary glands.

Free nuclear receptors were measured in anterior pituitaries from ovariectomized-adrenalectomized rats after extraction of purified nuclei with 0.4 M KC1 and incubation of the extract with 2.5 nM (3H)-estradiol (E2) during 1.5 h at 0-4 degrees C. High affinity, low capacity binding was present in untreated rats; receptor concentration doubled after E2 was given for 4 days, whereas acute (60 min) treatment was without effect. Prolonged exposure to diethylstilbestrol (3 months) down-regulated free as well as total nuclear receptors. Tamoxifen increased free nuclear receptors, induced the progestin receptor in cytosol, and inhibited E2-stimulated serum prolactin but not E2 stimulation of free nuclear receptors. Progesterone and testosterone had no effect on basal or E2-stimulated free nuclear sites, whereas dexamethasone reduced the former but not the latter. Furthermore, from 33 to 36% of free nuclear receptors bound to (3H)-E2, were retained in DNA-cellulose columns whether incubation with ligand was performed at low (0-4 degrees C) or high temperature (25 degrees C); DNA-cellulose binding was unchanged after short E2 but increased after 4 days of E2. These data suggest ligand as well as antiestrogen and corticoid regulation of free nuclear receptors for E2 in anterior pituitary. Free nuclear sites may be a fraction of total cell receptors which are in the transformed state and which bind more tightly to nuclei in vivo, as indicated by the results of DNA-cellulose binding in vitro.

Adrenalectomy↗
PubMed1985

p-Tyramine, a natural amine, inhibits prolactin release in vivo.

p-Tyramine, an endogenous amine with sympathomimetic action, is found in the mammalian hypothalamus. When injected ip, p-tyramine reduced serum PRL without altering LH and TSH serum titers in adult orchidectomized rats and rats subjected to ether or immobilization stress. The hyperprolactinemia achieved by this last procedure was inhibited by both tyramine and dopamine; tyramine produced the same effect as dopamine at a dose 5 times greater. When PRL levels were increased by pretreatment with alpha-methyl-p-tyrosine or haloperidol, once again both tyramine and dopamine lowered PRL titers. The hypoprolactinemic effect of p-tyramine was also observed in median eminence-lesioned animals, suggesting a pituitary site of action. These results show that low amounts of tyramine, a naturally occurring amine, can inhibit in vivo increases in PRL levels achieved physiologically or pharmacologically.

Animals↗
PubMed1985

Effect of median eminence lesions and hormonal replacement on the prolactin receptors in the adrenal gland and Langerhans islets from ovariectomized adult rats.

The effect of hyperprolactinemia induced by median eminence lesions (MEL) and ACTH and glucocorticoid replacement on prolactin (Prl) receptors was studied in the adrenal, isolated Langerhans islets and the liver. Adult rats were ovariectomized 15 days before MEL and they were divided in the following groups: 1) SHAM: injected with saline solution 3 times in alternate days; 2) MEL: saline solution; 3) MEL + ACTH: 50 micrograms: 10 IU/rat, s.c. (Synacthen) and 4) MEL + DEXA: 10 micrograms/rat (dexamethasone). For measuring total lactogenic binding sites an in vitro treatment of the membrane fraction with 4M MgCl2 was used. MEL originated a significant increase in Prl serum levels, which was not altered by injections of ACTH or dexamethasone. In contrast, serum corticosterone (B) levels in MEL rats were significantly lowered, and it was restored by ACTH. Unexpectedly, B levels increased when dexamethasone was administered to MEL rats. Prl receptors were diminished in the adrenal gland and Langerhans islets from MEL animals, as compared with the SHAM group. ACTH and glucocorticoid administration did not affect the pancreatic Prl receptors, while the adrenal gland exhibited a further lowering of Prl binding sites during ACTH treatment. Since no effect was found when dexamethasone was injected, a possible direct action of ACTH is suggested. On the other hand, Prl receptors were induced in the liver by MEL, and this action was abolished by dexamethasone and ACTH. Binding affinity in every tissue studied remained unchanged. Our data suggest that endogenous Prl is able to regulate its own receptors not only in the liver, but also in the adrenal gland and pancreatic islets.

Adrenal Glands↗
PubMed1984

High correlation between prolactinemia, 125-I hLH binding and progesterone secretion by an experimental luteoma.

Autoimplantation of an ovary, containing fresh corpora lutea, into the spleen of an ovariectomized rat is followed by strong luteinization and size increase of the grafted gonad. Thus, large amounts of luteal tissue for biochemical studies, and their histological controls are available. Furthermore, progesterone secretion can be easily determined in samples collected from the portal vein. Since prolactin has been implicated in the control of luteal tissue, the role of this hormone on hLH binding and progesterone secretion was determined. Different levels of endogenous serum prolactin were achieved by pharmacological treatments with neurotropic agents. Scatchard plots of 125-I hLH binding data derived from luteoma particulate fractions revealed the presence of one type of binding site with high affinity. At the same time as binding increased, prolactinemia augmented, with a high correlation (R:0.99) between prolactinemia and LH binding. Moreover, progesterone secreted by the luteoma increased as LH binding sites augmented (R:0,97). It is concluded that a high correlation between prolactinemia and LH binding, as well as between this last parameter and progesterone output exists in the experimental luteoma.

Animals↗
PubMed1984

A developmental study of adenohypophyseal dopaminergic receptors and of haloperidol-induced prolactin release in rats.

The ontogenesis of adenohypophyseal dopamine receptors, assessed by haloperidol-displaceable [3H]didydroergocryptine (DHE) binding of 1-, 12-, 20-, 28-day-old female rats was studied in correlation with the prolactin releasing effect of haloperidol (1 mg/kg), a dopaminergic antagonist. A specific dopaminergic receptor could be quantified at the time of birth (Bmax = 2.5 +/- 0.5 fmol/mg; Kd = 1.5 +/- 0.2 microM), anterior pituitary receptor density (fmol bound/mg) increased non-significantly henceforth and a slight ontogenic increase of Kd values was also observed. Haloperidol failed to increase prolactin in newborn female rats; at 4 days, a significant increase was evidenced, and from then onwards the response rose markedly with age. As sex differences in the dopaminergic modulation of prolactin release have been documented, the hyperprolactinemic effect of haloperidol in correlation with [3H]DHE binding in anterior pituitary of 28-day-old female and male rats was studied. Though the prolactinemic increment achieved by haloperidol was significantly higher in female than in male rats, [3H]DHE binding was not statistically different between sexes. These data indicate: (a) a specific binding site for [3H]DHE in anterior pituitary of female rats is present from the first postnatal days. From then onwards, a gradual but slight increment in both, Bmax and Kd for the dopaminergic agonist is observed until puberty; (b) at 28 days, no clear difference in Bmax and Kd is present in [3H]DHE binding between male and female rats; (c) by contrast, haloperidol shows a prolactin releasing effect that increases markedly with age in the female.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Sexual differences in the serotonergic control of prolactin and luteinizing hormone secretion in the rat.

The effects of serotonin on PRL and LH release were investigated in female and male rats under different experimental conditions. At a dose of 5 mg/kg ip, serotonin increased serum PRL titers in intact males and in females during diestrus and estrus; the levels attained in the male rats were much higher than in the females. At a lower dose (2.5 mg/kg) the PRL-releasing effect of serotonin was only evident in male rats. Thus, we chose this dose for the following experiments to investigate the apparent sexual difference. To evaluate the importance of the hormonal status characteristic of male and female in conditioning the serotonin effect, an experiment was performed in gonadectomized rats, untreated or treated with estradiol benzoate (EB), or testosterone propionate (TP). In the three hormonal conditions the sexual difference was maintained: serotonin released PRL in males and failed to do so in females. However, if males were castrated within 24 h of birth, and females androgenized by a single perinatal injection of TP, the sexual difference in adulthood were reversed; thus, androgenized females responded to serotonin and males castrated at birth failed to do so. These results suggest that a male differentiated brain is more sensitive to the PRL-releasing effect of serotonin, irrespective of the hormonal environment of the rat. On the other hand, serotonin increased serum LH in female rats in estrus and in adult ovariectomized rats treated with EB; but not in females in diestrus or in ovariectomized rats, treated with TP or untreated. Neither did it modify serum LH titers in male rats whether intact, orchidectomized, or orchidectomized plus steroids. However, if male rats were castrated a few hours after birth and then treated in adulthood with EB, serotonin effectively released LH. Thus, two components, estradiol and a feminine differentiated brain, may be necessary for the facilitatory action of serotonin on LH release. Since no sex differences were observed in the increase of serum serotonin after the injection of 2.5 mg/kg of the drug, it can be discounted that the differences described for the endocrine effect of the drug could be due to different levels of circulating indolamine achieved in male and female rats. Taken together, our results indicate that serotonergic control of anterior pituitary secretion is sexually differentiated and that it presents individual characteristics for PRL and LH release.

Aging↗
PubMed1983

Inhibition by naloxone of the serotonin-induced prolactin release in free-moving rats.

The effect of the opiate antagonist naloxone on serum prolactin after treatment with serotonin, arginine vasotocin (AVT) or melatonin was studied in prepubertal and adult unanesthetized rats. Prolactin was quantified in blood samples withdrawn through an intrajugular silastic cannula from undisturbed ovariectomized adult rats. After taking a basal sample, animals were injected through the cannula with naloxone (0.8 mg/kg) and 5 min later with serotonin creatine sulphate (6.4 mg/kg), AVT (20 micrograms/kg), melatonin (4 mg/kg) or saline; new samples were taken 15 and 30 min thereafter. Injection of serotonin was followed by a 10-fold increase of prolactin levels 15 min later; this increase was drastically reduced, although not abolished, by pretreatment with naloxone. In animals injected with saline, AVT or melatonin, no significant changes in serum prolactin were observed. In a second group of experiments, 30 day-old female rats injected with serotonin creatinine sulphate (10 mg/kg, i.p.) exhibited a 6-fold increase in serum prolactin 15 min after injection; this increment was reduced but not abolished by pretreatment with naloxone (5 mg/kg, i.p.). It is postulated that the prolactin releasing effect of serotonin is mediated, at least in part, by an opioid receptor.

Animals↗
PubMed1983

Changes in nuclear translocation of estradiol-receptor complex in anterior pituitary and uterus of rats with streptozotocin diabetes.

We have studied estradiol (E2) receptor nuclear translocation in anterior pituitary and uterus of ovariectomized control and diabetic rats one month after diabetes induction with Streptozotocin. Animals were pretreated with a low (0.5 microgram/100 g) or a high (25 micrograms/100 g) E2 dose 60 min before killing for the pituitary nuclear translocation. We observed that with the low E2 dose, nuclear translocation was reduced in pituitary from diabetic rats; the low dose given for 4 days also resulted in reduced induction of cytosolic progestin receptors in the pituitary and lower serum prolactin response in the diabetic group. With the 25 micrograms/100 g E2 dose, E2-receptor translocation, and the biological activity of E2 (induction of progestin receptors and serum prolactin response) were in the normal range. Serum E2 in controls and diabetics treated with E2 were not different. In the uterus, both low and high E2 doses given for 4 days resulted in significantly reduced nuclear translocation and uterine weight increment in the diabetic animals. These results suggest a brain-pituitary disturbance in addition to a peripheral (uterine) relative insensitivity to sex hormones as contributing factors to the reproductive failure of diabetic animals.

Animals↗
PubMed1983

Serotoninergic involvement in the cimetidine-induced prolactin release.

Pharmacological manipulation of H1 and H2 histamine receptors clearly indicates their participation in control of anterior pituitary secretion by the brain. Of particular interest is the PRL-releasing effect of H2 histamine receptor blocking agents like metiamide and cimetidine. The aim of the present study was to determine whether serotoninergic pathways, which exert a well known releasing effect on PRL secretion, were involved in the PRL-releasing action of cimetidine. As our first approach, the PRL-releasing effect of cimetidine was determined in developing male and female rats. Cimetidine failed to increase PRL in rats of 1 and 4 days of age. From 12 days onwards, the drug was able to cause a PRL increment in both sexes. There was a significant release of PRL at 20 and 28 days of age, and the response was greater in male than in female rats. The ontogeny of the cimetidine action, both in timing and sex differences, showed a close similarity with the development of the serotoninergic control of PRL secretion, and it was in clear contrast with the maturation of other controlling mechanisms, dopaminergic and TRH. In a second set of experiments, adult male rats were used. Methysergide, a serotonin receptor blocker, used in a dose and given by a route so that it did not modify the basal level of PRL, was able to completely prevent the PRL release evoked by cimetidine. Administration of p-chlorophenylalanine, a drug which reduces serotonin synthesis, was followed by a significant decline in the indole content of a portion of the brain which included the brain stem, the hypothalamus, and the preopticsuprachiasmatic area; and by a blockade of the PRL-releasing effect of cimetidine. Treatment of adult male rats with cimetidine, methysergide, or serotonin did not modify serum LH. It is concluded that a major serotoninergic input is involved in the PRL-releasing effect of cimetidine.

Aging↗
PubMed1982

Further studies on the effect of cimetidine and other neurotropic drugs on rat serum prolactin.

The hyperprolactinemic effect of H2 histamine receptor antagonists has been described in the rat and in humans. The present study was undertaken to explore more fully the hyperprolactinemic action of cimetidine, and its interrelationship with other neurotropic agents. Adult ovariectomized estrogen-primed rats were injected with mepiramine, diphenhydramine, pilocarpine, atropine, dopamine, cimetidine or saline as control, at different sequences and the effect on serum prolactin was determined. The effect of cimetidine on prolactin release "in vitro" by hemipituitaries of estrogenized male rats during a short time incubation period, was also investigated. Our results indicate that cimetidine is able to release prolactin and that this effect is not prevented by atropine or the classical antihistaminergic agents mepiramine and diphenhydramine. Both pilocarpine and dopamine inhibit the prolactin release due to cimetidine. The hypoprolactinemic action of pilocarpine was completely blocked by atropine, but not by mepiramine or diphenhydramine. Finally, cimetidine was unable to modify significantly the prolactin release by incubated pituitaries. It is postulated that cimetidine acts mainly at the brain and that the hyperprolactinemic effect is not mediated by muscarinic or H1 histaminergic receptors. This action can be prevented by drugs such as dopamine that are able to act on the lactotroph, and also by pilocarpine, probably by stimulating a prolactin inhibiting pathway.

Animals↗
PubMed1982

Comparative maturation of the regulation of prolactin and thyrotropin by serotonin and thyrotropin-releasing hormone in male and female rats.

The aim of this study was to compare the effects of TRH, serotonin, and haloperidol on the secretion of PRL and TSH in male and female rats from birth to puberty. Serum PRL in males and females was low from birth to 20 days; it then increased gradually until puberty. TSH did not change significantly throughout the period studied. The PRL-releasing effect of serotonin became evident at 12 days, and at all times when the response occurred, it was greater in males than in females. This was also observed in adult rats in which 2.5 mg/kg ip serotonin caused an increase in serum PRL in males but not in diestrous females. Serotonin did not modify TSH at any age. On the other hand, TRH induced the release of TSH and PRL from the first day of life and no sex difference was observed. Haloperidol caused release of PRL from birth, and the effect increased significantly with age. The PRL increase induced with haloperidol was greater than that obtained with TRH used in supramaximal doses. A clear sexual difference became evident on day 20, the PRL-releasing effect of haloperidol being more pronounced in females than in males. Haloperidol did not modify TSH values. It is concluded that the mechanisms by which TRH and dopamine regulate PRL secretion mature earlier than those influenced by serotonin. Sexual differences in the manifestation of these mechanisms were observed, the male being more sensitive to serotonin and the female to haloperidol. TRH causes release of TSH from birth; the serotoninergic and dopaminergic pathways are not of paramount importance in the regulation of TSH in the prepubertal rat.

Age Factors↗
PubMed1982

gamma-Aminobutyric acid receptors in anterior pituitary and brain areas after median eminence lesions.

Previous results have indicated that the median eminence (ME) plays a key role in the regulation of estrogen and dopamine receptors in the anterior pituitary (AP). Since 3H-labeled gamma-aminobutyric acid ([3H]GABA) receptors have been described in the pituitary as well as in the brain, the aim of the present work was to investigate whether those receptors are also under hypothalamic control. Ovariectomized adults rats were divided into two groups. In the first one, the ME was lesioned by an anodic current (MEL); the second group consisted of sham-operated controls. Animals were used 7-14 days thereafter to study [3H]GABA binding in a crude mitochondrial membrane fraction prepared from the anterior pituitary, the hypothalamic-preoptic suprachiasmatic area, or the frontoparietal cortex. Binding of [3H]GABA was a saturable process, with high affinity in all studied structures. In AP Scatchard analysis of the saturation curves indicated similar Kd values in sham and MEL rats; the maximal number of binding sites increased from 0.65 +/- 0.005 pmol/mg protein in controls to 1.05 +/- 0.006 pmol/mg protein in MEL rats (P less than 0.001). In the hypothalamus, Kd values were similar in both groups, but the maximum number of binding sites (Bmax) increased about 50% in MEL animals. In the frontoparietal cortex, Kd values were similar in control and lesioned animals; but the Bmax decreased by 40% after the lesion. Animals with lesions showed hyperprolactinemia and a reduction in serum levels of LH, FHS, and TSH. Thus, Kd values were of similar magnitude in all studied regions and were not altered by ME destruction. Bmax values in controls were higher in the cerebral cortex than in the hypothalamus and AP. After ME lesions, there was an increment of [3H]GABA binding in AP and hypothalamus and a reduction in cerebral cortex. The data indicate that the ME participates in the regulation of [3H]GABA binding in AP and also suggest that it plays a role in regulating GABA receptors in various regions of the brain.

Animals↗
PubMed1981

Effect of testosterone on the hypothalamic-pituitary-testicular axis of the old male rat.

Old rats show lower serum testosterone, a lower increase in serum LH either after orchidectomy or after LHRH stimulation, and a lower number of hCG binding sites in testis, compared to younger controls. Treatment with testosterone for 5 to 6 weeks was followed by an increment in the androgen serum levels of about 70% in adult, and of 170% in old animals, a reduction to about one half testicular weight in both groups, and an inhibition of similar magnitudes in the LH increase that followed castration or LHRH stimulation. Testosterone treatment reduced the binding sites for hCG in testis of young rats but did not correct the already low values observed in the old animals. It is suggested that similarities and differences occur in the hypothalamic-pituitary-testicular axis of young and old animals and that differences could be due to changes in set points regulation of the system and/or some intrinsic modification of the hormone producing mechanisms.

Animals↗
PubMed1981

Effects of bromocriptine on [3H]estradiol binding in cytosol of anterior pituitary.

The hypothalamus may control hormone receptors in the anterior pituitary either by a direct trophic effect or indirectly by regulation of serum pituitary hormone levels. Rats whose medial basal hypothalamus had been destroyed in order to suppress neural control of the gland showed a reduction in [3H]estradiol binding in the anterior pituitary and high serum PRL levels; both changes were reversed by treatment of the lesioned rats with daily injections of bromocriptine, a dopamine agonist. In nonlesioned animals, the same treatment did not modify significantly those parameters. In another hyperprolactinemic model (rats with anterior pituitaries transplanted under the kidney capsule), [3H]estradiol binding by the in situ pituitaries of the host rats was similar to that in the nongrafted controls. These results suggest that changes due to median eminence lesion are reversible and that bromocriptine is able to act as a substitutive therapy which restores binding of estradiol in glands whose receptors have been decreased by the effect of the lesion. High PRL levels due to pituitary transplant do not account for the observed changes in the pituitary estradiol binding.

Animals↗
PubMed1980

Changes in total and polymerized tubulin of the medial basal hypothalamus and adenohypophysis of castrated or hormone-injected rats.

Treatment of orchidectomized rats with LH, FSH or prolactin decreased the tubulin content of the medial basal hypothalamus (MBH), whereas FSH or prolactin augmented it in the adenohypophysis (AH). After castration, negative correlations existed between serum LH and total or polymerized MBH tubulin, whereas in the AH positive correlations were found. After estradiol-progesterone treatment of spayed rats a significant correlation was found between serum LH and the percentage of AH tubulin in the polymerized form.

Animals↗
PubMed1980

[3H]Dihydroergocryptine binding in anterior pituitary and prolactin secretion: further evidence of brain regulation of adenohypophyseal receptors.

Secretion of PRL by the pituitary gland is under tonic inhibitory control by tuberoinfundibular dopaminergic neurons. The aim of the present work was to assess the influence of the hypothalamus on the binding of [3H]dihydroergocryptine, a dopamine agonist, in the adenohypophysis and its role in the hypoprolactinemic action of exogenous dopamine. Serum PRL levels were elevated in ovariectomized adult rats with electrolytic lesions of the median eminence compared to levels in sham-operated animals; [3H]dihydroergocryptine binding to anterior pituitary was elevated from a control value of 161.2 +/- 7.7 to 229.0 +/- 10.0 fmol/mg protein in rats studied 7-21 days after placement of the lesion (P < 0.05). Scatchard analysis of [3H]dihydroergocryptine binding in lesioned and sham-operated animals indicated an increase of 62% in the number of binding sites without a change in binding affinity. In a second group of rats, with or without median eminence destruction, the effects of different doses of ip dopamine on serum PRL were determined. The hypoprolactinemic effect of each dose of the amine was more evident in median eminence-lesioned rats than in sham-operated controls. These results suggest that when hypothalamic influences on the anterior pituitary are removed, there is increased binding of dopamine by the gland and increased hypoprolactinemic effects of the exogenous amine. This indicates that receptors in the pituitary are under hypothalamic control, and this could be an important regulatory mechanism in neuroendocrine events.

Animals↗