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Biomedical subjects

M Lasaga

Publications and source records attributed to M Lasaga.

At least 37 records · Page 2Linked to original sources
PubMed1995

Role of nitric oxide in control of prolactin release by the adenohypophysis.

Nitric oxide synthase-containing cells were visualized in the anterior pituitary gland by immunocytochemistry. Consequently, we began an evaluation of the possible role of NO in the control of anterior pituitary function. Prolactin is normally under inhibitory hypothalamic control, and in vitro the gland secretes large quantities of the hormone. When hemipituitaries were incubated for 30 min in the presence of sodium nitroprusside, a releaser of NO, prolactin release was inhibited. This suppression was completely blocked by the scavenger of NO, hemoglobin. Analogs of arginine, such as NG-monomethyl-L-arginine (NMMA, where NG is the terminal guanidino nitrogen) and nitroarginine methyl ester, inhibit NO synthase. Incubation of hemipituitaries with either of these compounds significantly increased prolactin release. Since in other tissues most of the actions of NO are mediated by activation of soluble guanylate cyclase with the formation of cyclic GMP, we evaluated the effects of cyclic GMP on prolactin release. Cyclic GMP (10 mM) produced an approximately 40% reduction in prolactin release. Prolactin release in vivo and in vitro can be stimulated by several peptides, which include vasoactive intestinal polypeptide and substance P. Consequently, we evaluated the possible role of NO in these stimulations by incubating the glands in the presence of either of these peptides alone or in combination with NMMA. In the case of vasoactive intestinal polypeptide, the significant stimulation of prolactin release was augmented by NMMA to give an additive effect. In the case of substance P, there was a smaller but significant release of prolactin that was not significantly augmented by NMMA. We conclude that NO has little effect on the stimulatory action of these two peptides on prolactin release. Dopamine (0.1 microM), an inhibitor of prolactin release, reduced prolactin release, and this inhibitory action was significantly blocked by either hemoglobin (20 micrograms/ml) or NMMA and was completely blocked by 1 mM nitroarginine methyl ester. Atrial natriuretic factor at 1 microM also reduced prolactin release, and its action was completely blocked by NMMA. In contrast to these results with prolactin, luteinizing hormone (LH) was measured in the same medium in which the effect of nitroprusside was tested on prolactin release, there was no effect of nitroprusside, hemoglobin, or the combination of nitroprusside and hemoglobin on luteinizing hormone release. Therefore, in contrast to its inhibitory action on prolactin release NO had no effect on luteinizing hormone release. Immunocytochemical studies by others have shown that NO synthase is present in the folliculostellate cells and also the gonadotrophs of the pituitary gland. We conclude that NO produced by either of these cell types may diffuse to the lactotropes, where it can inhibit prolactin release. NO appears to play little role in the prolactin-releasing action of vasoactive intestinal polypeptide and substance P, but mediates the prolactin-inhibiting activity of dopamine and atrial natriuretic factor.

Amino Acid Oxidoreductases↗
PubMed1994

Involvement of hypothalamic substance P in the effect of prolactin on dopamine release.

In order to examine the role of hypothalamic SP in the feedback regulation of prolactin, we studied the effect of prolactin and dopamine on SP concentration and release, and the effect of SP on dopamine release. Hypothalamic fragments from male Wistar rats were incubated in the presence of prolactin, dopamine or SP under basal and K(+)-stimulated conditions. SP (10(-7) M) stimulated dopamine release, while dopamine (10(-7) M) decreased SP content and release. Prolactin (100 ng ml-1) increased SP content and release. An increase in hypothalamic SP content was also found during suckling. In addition, a specific antagonist for SP, Win 62,577, blocked the effect of prolactin and dopamine release. These results show an interaction between SP and dopamine at the hypothalamic level and suggest that SP could mediate the feedback action of prolactin on dopamine release.

Androstenes↗
PubMed1994

GABA transport and subcellular distribution in the rat anterior pituitary gland.

In this investigation we have studied the uptake of gamma aminobutyric acid (GABA) into anterior pituitary slices. Tissue:medium ratios of about 45:1 were obtained after a 30-min incubation. The process responsible for 3H-GABA uptake was temperature-sensitive and sodium-dependent. The kinetic constants of saturable GABA transport were: Km 4.141 microM and Vmax 0.973 pmol/min/mg protein, at 25 degrees C. The incorporation of GABA into anterior pituitary was inhibited by specific inhibitors of neuronal and/or glial uptake. The subcellular distribution of GABA was investigated by continuous sucrose density gradients and differential centrifugation. Most of the endogenous and labelled GABA was present in the soluble fraction. However, a small part of GABA was found in the particulate fraction. These observations indicate that the anterior pituitary gland is able to concentrate GABA which interacts with intracellular particles.

Animals↗
PubMed1991

Possible role of vasoactive intestinal peptide in the hyperprolactinemia induced by ethanol.

The effect of the blockade of endogenous VIP by injecting a specific rabbit anti-VIP serum (A-VIP) was studied in rats receiving an acute injection of ethanol. A-VIP administration decreased serum prolactin levels and reduced the hyperprolactinemia induced by ethanol. We also investigated the effect of the acute administration of ethanol on the concentration and release of VIP from the mediobasal hypothalamus. Ethanol decreased VIP concentration in the mediobasal hypothalamus, whereas it stimulated the in vitro K(+)-evoked release of VIP from this tissue. Conversely, ethanol increased VIP concentration in the anterior pituitary gland. The data indicate that VIP may be involved in the pituitary response to ethanol. The increased anterior pituitary VIP after ethanol may be due to an augmented release from the mediobasal hypothalamus.

Animals↗
PubMed1990

Ethanol-related changes in substance P in the hypothalamus and anterior pituitary.

The effect of the administration of a rabbit anti-substance P serum (ASPS) was studied in rats receiving an acute injection of ethanol. ASPS lowered serum prolactin levels and reduced the hyperprolactinemia induced by ethanol. ASPS also decreased LH serum levels in both saline- and ethanol-treated rats. The effect of ethanol on the concentration of substance P-like immunoreactivity (SP-LI) in the mediobasal hypothalamus and the anterior pituitary gland was also investigated. Ethanol reduced SP-LI in the mediobasal hypothalamus but increased it in the anterior pituitary gland. The presence of ethanol (50 mM) did not affect the K(+)-evoked release of SP-LI from either mediobasal hypothalamus or anterior pituitary gland, though it increased the SP-LI concentration remaining in this gland. These results indicate that ethanol increases the content of SP-LI in the anterior pituitary gland and suggest that substance P may be involved in the prolactin release induced by the acute administration of ethanol.

Animals↗
PubMed1990

Vasoactive intestinal peptide affects the GABAergic system in the hypothalamic-pituitary axis.

The effect of a specific antiserum against vasoactive intestinal peptide (VIP) on GABA in the hypothalamic-pituitary axis was studied. The administration of anti-VIP serum (A-VIP) increased anterior pituitary GABA concentration in control rats, but decreased this neurotransmitter in rats with hyperprolactinemia induced by acute or chronic treatments with estrogens, or by the implanting of anterior pituitary glands under the kidney capsule. Besides, the injection of the A-VIP serum in the morning in proestrous rats causes a decrease in anterior pituitary GABA concentration, measured in the afternoon of the same day. The in vitro effect of A-VIP and VIP on endogenous GABA release from hypothalamic fragments and on anterior pituitary GABA concentration was studied. A-VIP increased both basal and high K(+)-evoked GABA effluxes whereas VIP produced a decrease in evoked GABA efflux from hypothalamic fragments. Furthermore, A-VIP inhibited the normal degradation of GABA that occurs in the isolated gland whereas VIP increased it. These results suggest that VIP modifies hypothalamic GABA release and anterior pituitary GABA concentration.

Animals↗
PubMed1990

Effects of serotonin on the hypothalamic-pituitary GABAergic system.

The effects of serotonin (5-HT) and its precursor, 5-hydroxytryptophan (5-HTP) on the GABAergic system in the mediobasal hypothalamus (MBH) and the anterior pituitary were studied. The IP administration of 5-HTP produced a transient increase (only at 45 min after the injection) in glutamate decarboxylase activity (GAD) of MBH and in GABA concentration in anterior pituitary. Besides, 5-HTP administration increased the in vitro evoked GABA release from MBH. The administration of 5-HTP to hypophysectomized rats partially reversed the inhibitory effects of hypophysectomy on GABA concentration in MBH. We also examined the direct effect of 5-HT on some parameters on the hypothalamic GABAergic system. The presence of 5-HT in the incubation medium increased GAD activity and evoked GABA release from MBH. These observations indicate that the serotoninergic stimulation of the hypothalamic GABAergic system could be a direct effect which may, at least partially, be independent of the feedback mechanism induced by prolactin on the GABAergic neurons. The serotoninergic increase of prolactin secretion could be accomplished through stimulation of the hypothalamic GABAergic transmission.

4-Aminobutyrate Transaminase↗
PubMed1989

Estriol affects prolactin and LH secretion in rats.

The effects of estriol on serum prolactin (PRL) and LH levels, on the pituitary response to TRH and LHRH and on the synthesis and release of PRL from the anterior pituitary gland were investigated in female rats. The increase of serum PRL levels after estradiol administration was found to be associated with an increase of glutamic acid decarboxylase (GAD) and GABA-transaminase (GABA-T) in the hypothalamus. Thus, a study was carried out on the effects of estradiol and estriol on PRL secretion and on GAD, GABA-T and gamma-amino butyric acid (GABA) in the hypothalamus and the anterior pituitary. Under basal and TRH-stimulated conditions, estriol increased serum PRL levels, decreased basal serum LH levels, and increased the response to LHRH, in terms of LH release. Estradiol and estriol increased the synthesis and release of 3H-PRL from hemipituitary glands in incubations of pretreated animals. Both estrogens induced hyperprolactinemia, concomitantly with an increase of hypothalamic GAD and GABA-T activity. Estriol increased hypothalamic GABA concentration, but did not modify GABA concentration in the pituitary glands. Our results show that estriol, at relatively high doses, seems to be active in increasing PRL synthesis and release and in decreasing serum LH levels; it can also modify pituitary response to TRH and LHRH stimulation.

4-Aminobutyrate Transaminase↗
PubMed1989

Effects of passive immunization against vasoactive intestinal peptide on serum prolactin and LH levels.

Recent findings suggest that vasoactive intestinal peptide (VIP) may be a physiological regulator of prolactin secretion and may also be involved in the control of LH secretion. In the present work we have studied the effect of the blockade of endogenous VIP by means of the injection of a specific rabbit anti-VIP serum, in male and female rats with hyperprolactinemia. The administration of 0.5 ml of the VIP antiserum in ovariectomized rats given an acute or chronic treatment with 17 beta-estradiol induced a significant decrease in serum prolactin and LH levels as compared with estrogenized-control rats injected with normal rabbit serum. Anti-VIP serum also reduced serum LH levels in ovariectomized rats not treated with estrogens. The administration of the same antiserum decreased serum prolactin levels in male rats implanted with 2 anterior pituitary glands under the kidney capsule. On the other hand, the injection of the anti-VIP serum in the morning in proestrus rats brought about an increase in serum prolactin and LH levels in the afternoon of the same day. These results confirm previous data showing that VIP is a stimulator of prolactin release, and may also participate in the control of LH secretion in ovariectomized rats acting as a facilitatory factor. During proestrus however, VIP may act in an opposite way, inhibiting, rather than stimulating, prolactin and LH release.

Animals↗
PubMed1988

Effect of sex steroids on GABA receptors in the rat hypothalamus and anterior pituitary gland.

Our data indicate that sex steroids modify the number of GABA receptors, as detected by a [3H]muscimol binding assay, in the tuberoinfundibular GABAergic system. GABA binding was affected by chronic hormonal treatments in different ways depending on the sex of the rats and the steroids administered. Estradiol increased GABA binding in ovariectomized female rats while testosterone decreased the number of GABA binding sites in gonadectomized male rats. These results suggest a sex difference in the regulation of hypothalamic GABA receptors.

Animals↗
PubMed1988

Effect of ethanol on GABA uptake and release from hypothalamic fragments.

A study was performed on the effect of ethanol on the basal and K+-evoked efflux of endogenous GABA from rat hypothalamic fragments. The amount of GABA present in the medium and in the tissue was measured by radioreceptor assay. In vitro addition of ethanol (50 and 100 mM) enhanced the K+-evoked efflux of GABA in a Ca++-dependent manner, and increased tissue GABA content. Since K+-evoked outflow induced by ethanol was not affected by the presence of nipecotic acid, ethanol appears to alter the uptake of endogenous GABA. An inhibitory effect of ethanol on 3H-GABA uptake was observed under K+ depolarization. On the other hand, acute ethanol administration produced a decrease in basal and K+-evoked efflux from hypothalamic fragments and in tissue GABA concentration. Changes in GABA efflux may lie behind some of the neuropharmacological effects of ethanol.

Animals↗
PubMed1988

Possible mechanisms of action of ethanol-induced release of prolactin from rat anterior pituitary.

We have demonstrated previously that ethanol increases the in vitro synthesis and release of prolactin by the anterior pituitary gland. In the present study we have examined the possible role of calcium and calmodulin in the ethanol-stimulation of in vitro prolactin release from hemipituitary glands. We also investigated the effect of inhibitors of arachidonic acid metabolism on the release of prolactin induced by ethanol. In addition we studied the effect of ethanol on the release of prostaglandins and the conversion of arachidonic acid to hydroperoxides. Basal and ethanol-stimulated prolactin release was almost blocked completely by omitting calcium from the incubation medium. In vitro addition of calmodulin-blocking agents such as pimozide and trifluoperazine reduced basal and ethanol-induced prolactin release. Acetylsalicylic acid, an inhibitor of the cycloxygenase pathway, had no effect on prolactin release. Nordihydroguaiaretic acid, an inhibitor of the lipoxygenase pathway, blocked completely the release of prolactin induced by ethanol. Ethanol (5 and 10 mM) significantly increased the release of prostaglandin E2 and prostaglandin F2 alpha and the conversion of [14C]arachidonic acid to 5-hydroxyeicosatetraenoic acid. The results of this study show that ethanol increases prolactin release by a calcium-dependent mechanism. Besides, our data suggest that arachidonic acid metabolism is involved in ethanol-stimulated prolactin secretion and that lipoxygenase pathway metabolites are at least partially responsible for this effect.

Animals↗
PubMed1987

Effect of an anti-substance P serum on prolactin and gonadotropins in hyperprolactinemic rats.

The effects of the acute injection of a rabbit anti-substance P serum (ASPS) were studied in normal rats and rats with hyperprolactinemia induced by 5-hydroxytryptophan and estradiol given as a short or chronic treatment. The anti-substance P serum decreased the release of prolactin induced by 5-hydroxytryptophan when this serotonin precursor was injected 24 h, but not 1 h, after the administration of the antiserum. ASPS reduced the hyperprolactinemia induced by short and chronic treatment with estradiol in castrated rats. This effect was observed 24 h after the injection of the antiserum. On the other hand, the injection of ASPS induced a significant decrease in LH levels in serum of intact male rats injected with 5-hydroxytryptophan 24 h after ASPS, and in castrated rats treated with short-term and chronic administration of estradiol, 24 h after the injection of the antiserum. These results suggest that substance P may have a role in the control of prolactin secretion and could play a part in the hyperprolactinemic effects of estradiol. On the other hand, substance P, under certain circumstances, may stimulate LH release.

5-Hydroxytryptophan↗
PubMed1987

The effect of prolactin on glutamate decarboxylase activity and GABA concentration in hypothalamic slices.

The effect of prolactin on the activity of GABA-related enzymes and GABA concentrations were studied in hypothalamic slices incubated in vitro. After short periods of incubation (up to 40 min), prolactin (0.25 micrograms/ml) added to the incubation medium produced a significant increase (21% at 20 min of incubation) in glutamic acid decarboxylase (GAD) activity in the hypothalamic slices. A higher concentration of prolactin (1.0 micrograms/ml) produced a slight but significant decrease (8% at 20 min of incubation) in hypothalamic GAD activity. However, after longer periods of incubation (over 8 hr), both doses of prolactin induced a sustained increase in hypothalmic GAD activity, a response which depends upon protein synthesis. No changes were observed in GABA-transaminase (GABA-T) activity of hypothalamic slices incubated in the presence of prolactin. Prolactin decreased GABA concentration in the hypothalami incubated for 10 hr and, at the same time, increased GABA release into the medium. These results indicate that prolactin modifies the synthesis and release of hypothalmic GABA and suggest the existence of a feedback mechanism that prolactin may exert directly at the hypothalamic level.

Animals↗
PubMed1987

Mechanisms of endogenous GABA release from hypothalamic fragments. Effect of prolactin.

The efflux of endogenous gamma-aminobutyric acid (GABA) has been studied using small hypothalamic fragments containing arcuate-paraventricular nuclei and median eminence from the rat brain. The amount of GABA present in the medium and the tissue GABA content were quantified by radioreceptor assay. The endogenous GABA efflux was found to be dependent upon the Ca2+ and K+ concentrations in the incubation medium, and it required synthesis of GABA, indicating neuronal origin of the released neurotransmitter. Nipecotic acid, an inhibitor of neuronal and glial uptake, prevented reuptake of released GABA. Prolactin in concentrations of 250 and 1,000 ng/ml augmented the K+-evoked efflux of GABA. The effect of prolactin was dependent on the presence of Ca2+ and on the synthesis of GABA. In addition, prolactin seems to alter the reuptake of endogenous GABA and the uptake of [3H]-GABA. In conclusion, these results suggest that prolactin may influence its own secretion by stimulating the release of hypothalamic GABA, both through an increase of its synthesis and a modification of its reuptake.

3-Mercaptopropionic Acid↗
PubMed1985

Effect of GABA-T inhibitors on prolactin secretion in vitro.

A study was made of the effect of GABA-transaminase (GABA-T) inhibitors on the in vitro release of prolactin by pituitaries of male and female rats. Aminooxyacetic acid (AOAA) and gamma-acetylenic GABA (GAG) added to the incubation medium decreased prolactin release from both male and female rat pituitaries. Additive effects on prolactin release were only observed when male rat pituitaries were incubated with AOAA plus GABA. Prolactin concentration in the pituitary gland was also decreased by AOAA in both sexes. The present results lend support to the idea of an inhibitory action of GABA on prolactin release by the pituitary gland.

4-Aminobutyrate Transaminase↗