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C Libertun

Publications and source records attributed to C Libertun.

At least 55 records · Page 3Linked to original sources

Octopamine and phenylethylamine inhibit prolactin secretion both in vivo and in vitro.

Trace amines are a group of biogenic amines that are present in neural tissue in concentrations ranging from 0.1 to 100 ng/g. In the present work, we examined the action of two trace amines, octopamine and phenylethylamine, which are found in the hypothalamus, on pituitary hormone secretion in different experimental situations in vivo and in dispersed anterior pituitary cells. Both octopamine and phenylethylamine decreased high prolactin levels due to swimming or immobilization stress without affecting other adenohypophysial hormones. With regard to the hypoprolactinemic potencies in the immobilization stress model, it was observed that p-tyramine, another trace amine, was as potent as octopamine. Phenylethylamine was the least effective. To evaluate the site of action of the effect described, the three trace amines were tested in dispersed anterior pituitary cell cultures in vitro. Tyramine and octopamine reduced prolactin secretion in a concentration-dependent manner, at concentrations of 10(-8) to 10(-5) M, whereas the hypoprolactinemic effect observed for phenylethylamine was very weak. In pharmacologic experiments, neither octopamine nor phenylethylamine reduced prolactin release when dopaminergic receptors were blocked. This could mean that their hypoprolactinemic action was mediated through the release of dopamine, or it could be a direct action at a dopaminergic receptor. This is the first description of a specific endocrine action both in vivo and in vitro for octopamine and phenylethylamine. Further studies are needed to ascertain the physiologic or pathologic implication of these findings.

Analysis of Variance↗

Further evidence for the inhibitory action of baclofen on a prolactin-releasing factor.

The mechanism of action of a specific gamma-aminobutyric acid B receptor agonist, beta-p-chlorophenyl-gamma-aminobutyric acid or baclofen, in its inhibitory action on prolactin release, was studied. Dose-response studies of the effect of baclofen on prolactin (PRL) secretion were performed in stressed male rats. Furthermore, the action of the drug was evaluated in (i) rats treated with haloperidol or alpha-methyl-p-tyrosine, (ii) stressed or suckled rats pretreated with sulpiride, and (iii) animals treated with serotonin, alone, or with alpha-methyl-p-tyrosine. Baclofen showed a clear dose-dependent inhibition of prolactin secretion in males under stress. The drug was unable to inhibit the prolactin release induced by haloperidol or alpha-methyl-p-tyrosine, although it reduced the PRL secretion induced by serotonin. It also inhibited PRL release in sulpiride-pretreated stressed or suckled rats. These results suggest that the dose-dependent effect of baclofen on PRL secretion is the consequence of an inhibition exerted on the prolactin-releasing factor component of the neuroendocrine responses evoked by stress or suckling, possibly acting at the serotonergic system.

Animals↗

Ontogenic studies of the neural control of adenohypophyseal hormones in the rat: gonadotropins.

1. Serotonergic, dopaminergic, and opioid systems controlling luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion develop with particular characteristics in the male and female prepubertal rats. 2. Serotonergic pathways evoke a maximal release of LH and FSH in female rats from day 12 to day 20 of age, but not in males of the same age. 3. Antidopaminergic drugs increase LH and FSH levels only in the female infantile rats. This effect is absent at birth and disappears after 20 days of age. 4. Naloxone markedly increases gonadotropins in 12-day-old females. 5. On the other hand, in 12-day-old male rats some neurotropic drugs such as diazepam could enhance LH levels, the effect being absent at other ages or in female littermates. 6. A period of high sensitivity of gonadotropins to neurotropic drugs is present during the second and third weeks of life of the rat and it is related to the sexual differentiation of the brain.

Animals↗

Prolactin-releasing effect of tryptolines in the developing and adult male and female rats.

The developmental prolactin-releasing effect of Tryptoline (T), Methoxytryptoline (MT) and Hydroxytryptoline (OHT) was examined comparatively in male and female rats. A single injection of T 15 mg/Kg increased serum prolactin in both sexes; the increase was significant from day 20 onwards. OHT evoked a sharp rise in 12 day-old rats and the releasing effect increased with age, both in males and females. No significant sex differences were observed in T or OHT treated rats. MT caused an increment in prolactin secretion in male rats and this action increased with age. The releasing effect of MT was not significant in females, even at 38 postnatal days. In adult animals, the tryptolines (15 mg/Kg) were able to increase serum prolactin in males and in females in diestrous; a dose of 5 mg/Kg of T was only effective in adult male rats. The prolactin-releasing effect was drastically reduced by orchidectomy and by ovariectomy. LH, FSH and TSH were not modified by any treatment. The present results show for the first time the ontogeny of the prolactin-releasing effect of tryptolines in male and female rats and that this effect depends on the presence of gonadal secretions in adults.

Aging↗

Ovarian follicle-stimulating hormone binding changes associated with the reinstatement of ovulatory cycles after lactation interruption in the rat.

The aim of this work was to study the endocrine changes that occur during the reinstatement of the ovulatory cycles after lactational infertility in the rat. Hormonal patterns and specific binding of [125I]FSH to ovaries of lactating rats that kept their pups (LRP) or were separated from their pups on day 13 postpartum (LRX) were studied on days 13-16 postpartum. In LRP rats gonadotropin levels remained low and unvarying throughout the experiment; PRL levels were high in the morning, low at 1300 h, and then surged in the afternoon. Estradiol levels were very low in LRP rats in serum as well as in ovarian homogenates, and progesterone levels decreased gradually from days 13 to 16. No changes in either receptor number or dissociation constants (Kd) were observed in [125I]FSH binding to ovaries of LRP rats. In LRX rats, LH peaked on the afternoon of day 15 (P less than 0.05). FSH decreased from morning levels on day 13 to morning levels on day 15, and then peaked at 1600 h on day 15 (p less than 0.05). PRL decreased rapidly (day 13 1600 h levels significantly lower than day 13 1100 h levels), then remained low and peaked on the afternoon of day 15 (P less than 0.05). IN LRX rats progesterone levels decreased more markedly than in LRP rats and then surged in the afternoon of day 15. Serum estradiol levels rose significantly in the morning of day 15, while ovarian homogenate estradiol titers had already risen on the morning of day 14. Significant increases in number of [125I]FSH-binding sites and Kd values were observed in LRX rats on day 15 postpartum. These results clearly show that litter removal at midlactation (day 13) induces the reinstatement of hormonal cyclicity, and this is accompanied by changes in ovarian FSH receptors.

Animals↗

Developmental changes in FSH secretion induced by 5-hydroxytryptophan, naloxone and haloperidol in male and female rats.

Follicle-stimulating hormone (FSH) secretion is increased in the immature female rat from day 5 to days 17-18 of life, and decreases steadily thereafter until puberty. It has been reported that estradiol negative feedback and inhibin-like peptides are low during this period, while luteinizing hormone (LH) and FSH sensitivity to LH-releasing hormone (LHRH) are maximal. It was therefore of interest to study the effects of some neurotropic drugs on FSH release at 12 days of age, and to compare their effects at 1 and 20 days. Besides, as developmental patterns and regulation of FSH are different in male and female rats, the experiments were carried out using male and female littermates. The drugs chosen were haloperidol, 5-hydroxytryptophan and naloxone. These drugs release LH in the infantile female rat, the effect decreasing or disappearing as the animal matures; no effects of these drugs have been reported on FSH release in infantile rats to the present time. It was found that haloperidol (0.25 mg/kg), naloxone (2 mg/kg) and 5-hydroxytryptophan (50 mg/kg) markedly increased the already high titers of FSH in the 12-day-old female rat. This effect could not be discerned in newborn rats, and had disappeared at 20 days of age. Male littermates failed to respond at any age. When adult male and female rats in diestrus were tested, all drugs at the chosen doses were ineffective in altering FSH release. These data suggest that the infantile female rat represents an interesting physiological model to evaluate the neural regulation of FSH in a situation in which inhibitory signals provided by inhibin and estrogen in later life are diminished.

5-Hydroxytryptophan↗

Diazepam: endocrine effects and hypothalamic binding sites in the developing male and female rat.

The ontogeny of diazepam's endocrine effects in male and female rats, and of 3H-diazepam binding in the hypothalami of both sexes was studied. Diazepam inhibited basal prolactin levels in 38 day-old male rats and, if prolactin levels were stimulated by Haloperidol the inhibition occurred in 28 day-old males, indicating that the hypoprolactinemic effect of the drug could be evidenced earlier if prolactin titers were high. The prolactin inhibition in females did not reach statistical significance at any studied age. Diazepam significantly released LH only in male rats at 12 days, showing thus, a period of special sensitivity of LH release to the drug. Benzodiazepine-hypothalamic binding sites increased in number from birth to puberty, reaching a plateau at 20 days of age. No sexual differences or changes in affinity were found throughout the studied period. These results suggest that the maturation of diazepam's hypoprolactinemic effect could be partially related to the increase in hypothalamic binding sites, whereas the sexual differences observed in diazepam's endocrine actions could be due to sexual differentiation of endocrine control mechanisms.

Animals↗

Chronic activation of dopamine receptors in the female infantile rat: effect on hypophyseal hormones and on the onset of puberty.

In the female rat the period from days 7-20 of age is special with regard to regulation of hypophyseal hormone secretion. This period is characterized by high FSH levels and the occurrence of sporadic LH peaks. As it has been reported that haloperidol could enhance both gonadotropins at 12 days of age and not at later ages, it was of interest to treat rats during the infantile period with pergolide, a dopaminergic agent of long action, and evaluate its effect on hormone levels and puberty onset. Three different schedules of drug injections were applied: 1) daily injections (0.05 mg/kg.day) on days 1-10, 2) daily injections on days 5-14, and 3) daily injections on days 11-20. It was found that only animals treated with daily injections of pergolide on days 11-20 showed an advance in the age of vaginal opening and first estrus compared to distilled water-injected controls. Thus, the rest of the experiments were performed using injection schedule 3. In this group of animals serum LH and FSH levels were decreased 3 and 6 days after the beginning of pergolide treatment (13 and 16 days of age); at 19 days of age pergolide did not modify gonadotropin levels. One day after the end of pergolide treatment (day 21 of age), there was a rebound in LH levels in drug-injected rats, and a nonsignificant increment in FSH levels was observed. There were no differences in serum gonadotropin levels on days 22, 23, and 25 or peripubertally (29, 33, or 36 days of age). On the other hand, pergolide did not significantly modify PRL levels during the treatment, probably due to the already low values of PRL at these ages. Furthermore, PRL levels were not different between control and pergolide-injected rats at all other ages studied. After puberty onset, animals were observed for eight consecutive cycles, and both groups cycled regularly. Furthermore, PRL and gonadotropins levels were similar at diestrus and proestrus. To evaluate if pergolide treatment during the infantile period had caused permanent alteration in dopamine receptor sensitivity, animals were injected with haloperidol (0.1 or 0.25 mg/kg), and PRL release was evaluated. There were no differences in the hyperprolactinemic effect of the drug between groups. Finally, gonadotropin sensitivity to LHRH was similar in adult female rats in proestrus of both groups. The present results suggest that chronic activation of dopamine receptors during the infantile period evokes specific responses on gonadotropin secretion and advances the age of puberty onset.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Differential responsiveness of LH and prolactin to p-tyramine in male and female rats.

The effect of p-tyramine, a natural amine which is found in the rat brain in trace amounts, was evaluated for its capacity to influence LH and prolactin secretion in male and female rats under different hormonal conditions. p-Tyramine (40 mg/kg ip) was ineffective in modifying LH levels in either female or male rats which had been gonadectomized for 2 days, but if the animals were injected with 12.5 micrograms of estradiol benzoate (EB) on the day of castration, p-tyramine was able to release LH in female but not in male rats. To evaluate whether early androgenization of brain structures which control LH secretion was involved in the sexual difference observed, p-tyramine was tested in female androgenized rats (200 micrograms of testosterone propionate on the day of birth), and in male rats castrated at birth. The trace amine was ineffective in altering LH levels in both experimental models, even if rats were pretreated with EB as control females. On the other hand, p-tyramine inhibited prolactin secretion in male rats pretreated with EB, and not in similarly treated female rats. The present results suggest that p-tyramine may be involved not only in prolactin regulation as it has been previously shown, but also in LH control, and that the hormonal response to this amine is sexually differentiated in the rat.

Animals↗

Natural and artificially induced ovulatory models related to lactation in the rat: role of prolactin.

The presence and the importance of a preovulatory prolactin (PRL) peak was determined in four, natural or artificially induced, ovulatory models related to lactation in the rat. Gonadotrophin peaks were determined in the afternoon preceding ovulation in four models: postpartum ovulation (PPO), ovulation after the lactational period (AL) (natural models), ovulation after litter removal at midlactation (ML), and ovulation in lactating rats (LR) (artificially induced models). In PPO, AL, and ML rats a preovulatory PRL surge was detected, showing that its presence is a common characteristic of ovulation in the rat. Bromocriptine inhibition of PRL levels in PPO and AL rats did not modify the percentage of rats which ovulated. In contrast, this treatment was able to significantly increase ovulation percentage in ML rats. Moreover, in LR rats strong dopaminergic inhibition of PRL levels, induced by pergolide, was necessary for ovulation to take place, but if pergolide-treated rats were injected with ovine PRL ovulation was completely inhibited. These data suggest that while a PRL surge seems to be always present in natural ovulatory models, it is not essential for ovulation to take place. On the other hand, in artificially induced ovulatory models, suppression of prolactinemia is able to induce ovulation or to increase the percentage of rats which ovulated. This effect of PRL on ovulation may be direct or indirect.

Animals↗

Further evidence for endogenous hypothalamic serotonergic neurons involved in the cimetidine-induced prolactin release in the rat.

The aim of the present work was to further explore the possible relationship between the prolactin-releasing effect of cimetidine and hypothalamic serotonergic neurons controlling pituitary hormone secretion. In a first approach, the prolactin-releasing effect of the drug was determined in adult male rats with total deafferentation of the hypothalamus. Cimetidine injection (60 mg/kg) produced a significant rise in prolactin, but not in luteinizing hormone (LH), both in deafferented rat and in sham-operated controls; by 15 min there was a 5-6 fold increase in prolactin titers. Methysergide, a serotonin receptor blocker, used in a dose (2.5 mg/kg), route (i.p.) and time (50 min earlier) which did not modify the hormone basal level in rats with total deafferentation of the hypothalamus, was able to prevent completely the prolactin release evoked by cimetidine. The same preventive effect on prolactin release was observed with the serotonin receptor blocker ketanserin (5 mg/kg, i.p., 30 min earlier). It is concluded that the prolactin-releasing effect of cimetidine is located at a hypothalamic level related to serotonergic neurons.

Animals↗

Sexual differences in the dopaminergic control of luteinizing hormone secretion in the developing rat.

The aim of the present study was to compare the effect of haloperidol on the secretion of luteinizing hormone (LH) in male and female immature rats. At 12 days of age, haloperidol significantly released LH in females but not in males. The same results were obtained using sulpiride. The LH-releasing effect of haloperidol diminished with age; in 28-day-old rats it could not be evidenced. The influence of early organization of brain structures controlling LH secretion on this effect was then studied. Neonatally androgenized females failed to respond at 12 days of age and in neonatally castrated males the effect of haloperidol on LH followed the same pattern as in normal females. We conclude that the dopaminergic system plays an important inhibitory role in the control of LH in infantile females and not in males, and that this sexual difference depends on early differentiation of the brain.

Animals↗

Neuroendocrine changes in female rats born from streptozotocin-diabetic mothers.

In adult female rats born from Streptozotocin-diabetic mothers, blood glucose measured under basal conditions or 30 min after glucose administration was similar to controls; however at 180 min 50% of offspring from diabetics was moderately hyperglycemic whereas 100% of controls were normoglycemic. The time of vaginal opening, and after maturity, the number of rats with regular estrous cycles was in the range of controls. After ovariectomy, control rats receiving estradiol showed a sharp increase of serum LH at 4 pm following progesterone treatment at 10 am, while rats born from diabetic mothers failed to modify serum LH. Estradiol receptors in cell nuclei and cytosolic progestin receptors were determined in anterior pituitary, hypothalamus and preoptic area of rats subjected to a 4-day estradiol treatment. Changes were statistically significant in the hypothalamus only, in that rats born from diabetic mothers showed reduced induction of progestin receptors coupled to increased binding of (3H)-estradiol in cell nuclei. These findings bring support for a hypothalamic defect in rats born from diabetic mothers, the reduction of hypothalamic progestin receptors being reflected in the reduced sensitivity to the positive feedback action of progesterone to release LH.

Animals↗

Prolactin inhibition by p-tyramine in the male rat: site of action.

In a previous report, a consistent hypoprolactinemic effect of p-tyramine was observed in male rats under several experimental conditions in vivo. In the present experiments the action of p-tyramine on PRL release in vitro, or after challenge with different hyperprolactinemic drugs (serotonin, morphine, and TRH) was tested. Furthermore the participation of octopamine, a metabolite of tyramine, was evaluated with regard to the hypoprolactinemic action of the amine. P-Tyramine inhibited PRL release from hemipituitaries incubated in vitro at doses of 10(-4) and 10(-6) M (inhibition to 31% and 59% of control values, respectively). When tested for its ability to displace [3H]spiperone binding in vitro to a crude fraction of anterior pituitary membranes it was found that it did not compete with the D2 receptor labeled by [3H]spiperone, even at the concentration of 10(-4) M. P-Tyramine (40 mg/kg) antagonized the elevation of serum PRL levels by morphine, serotonin, and TRH. On the other hand, octopamine, which is formed from tyramine, also inhibited high PRL values found after stress, though the effective dose was higher than that of tyramine. Pretreatment with diethyldithiocarbanic acid, which inhibits conversion of p-tyramine to octopamine, did not modify the effect of tyramine in stress. The present results indicate that tyramine can inhibit PRL release due to certain drugs, by acting directly at the pituitary level. It does not displace [3H]spiperone binding from anterior pituitary membranes, and octopamine which lowers PRL release itself, cannot account for the effect of tyramine.

Animals↗

Baclofen, a GABA derivative, inhibits stress-induced prolactin release in the rat.

The effect of baclofen, beta-(4-chlorophenyl)GABA, on prolactin secretion was investigated in rats under several experimental conditions. In adult male rats subjected either to immuobilization, ether, swimming or cold stress there was a rapid increase of serum prolactin levels; acute pretreatment with baclofen, 10 mg/kg i.p. inhibited the hormone response to all these stresses. The same blocking effect of the drug was observed in prepubertal male and female rats and in adult gonadectomized animals. In basal conditions, i.e. in undisturbed male rats, baclofen did not change the hormone titers significantly. Taken together our results indicate that baclofen blocks prolactin release when release of the hormone is dynamically stimulated by stress and this effect is relatively independent of the endocrine status of the rat.

Animals↗

Ontogenesis of [3H]serotonin binding sites in the hypothalamus of the female rat: relation to serotonin-induced LH release in moxestrol-pretreated rats.

The release of luteinizing hormone (LH) evoked by exogenous serotonin (5 mg/kg, i.p.) was measured at different developmental ages in the female rat. Since LH response to serotonin is modulated by estrogen, moxestrol, a synthetic compound which does not bind to alpha-fetoprotein, was administered 48 h before serotonin or saline injections. Serotonin was ineffective in releasing LH in 5-day females pretreated with moxestrol; the response increased abruptly at 12 and 18 days and from then onwards decreased gradually. This is in clear contrast to the development of the serotonin-induced prolactin release, which is absent in the first postnatal week, becomes evident on day 12 and increases gradually as the rat approaches puberty. In a second group of experiments, the ontogenesis of hypothalamic-preoptic suprachiasmatic [3H]serotonin binding was studied in 5-, 16-, 27- and 37-day-old female rats. A specific serotonergic binding site could be quantified at 5 days (Bmax 4.31 : 1.89 fmol/micrograms DNA; Kd: 2.74: 1.17 nM). A gradual increase of both Bmax and Kd was observed as the animal matured: the number of binding sites almost doubled from day 16 to day 27, and increased even further by 37 days (Bmax 24.21 : 5.16 fmol/micrograms DNA). These data indicate: a specific [3H]serotonin binding site in hypothalamic-preoptic suprachiasmatic area is present in the first postnatal week of the female rat; Bmax and Kd values increase from 5 to 37 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

beta-(-4 Chlorophenyl) GABA (baclofen) inhibits prolactin and thyrotropin release by acting on the rat brain.

Baclofen, a GABA B agonist, inhibits prolactin release due to different kinds of stress. In the present study its effect was evaluated in several endocrine experimental situations to explore the specificity of this effect, as well as the site of action of the drug. Baclofen significantly inhibited prolactin and thyrotropin outputs induced by 25 min of suckling, without altering milk ejection or LH secretion. The effect was also tested in median eminence-lesioned rats and in in vitro incubations. Baclofen did not modify prolactin levels in rats in which brain control of the pituitary secretion was eliminated by destruction of the median eminence, and it did not inhibit prolactin or thyrotropin secretion from incubated hemipituitaries. It is postulated that baclofen inhibits prolactin and thyrotropin secretion by acting on GABA B receptors related to the brain control of pituitary secretion.

Animals↗