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Biomedical subjects

L Debeljuk

Publications and source records attributed to L Debeljuk.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1987

Effect of [D-Trp6]LHRH infusion on prolactin secretion by perifused rat pituitary cells.

The effect of a superactive agonistic analog of luteinizing hormone-releasing hormone (LHRH), [D-Trp6]LHRH on prolactin (PRL) secretion by perifused rat pituitary cells was investigated. Constant infusion of [D-Trp6]LHRH (0.5 ng/min) for 2-3 h elicited a significant decrease in PRL secretion by these cells. This decrease in PRL release started ca. 30 min after the beginning of the infusion with the LHRH analog and lasted up to 1.5-2 h. [D-Trp6]LHRH significantly stimulated luteinizing hormone (LH) secretion during the first 30 min of peptide infusion; thereafter, LH levels began to return to control values. In animals pretreated in vivo with 50 micrograms of [D-Trp6]LHRH (s.c.) 1 h before sacrifice, PRL secretion by the rat pituitary cell perifusion system was significantly lower than vehicle-injected controls throughout the entire [D-Trp6]LHRH infusion period. On the other hand, thyrotropin-releasing hormone (TRH)-stimulated PRL secretion was slightly, but significantly imparied by [D-Trp6]LHRH infusion, while dopamine (DA) inhibition of PRL release was unaffected by this same treatment. These results reinforce previous observations of a modulatory effect of [D-Trp6]LHRH, probably mediated by pituitary gonadotrophs, on PRL secretion by the anterior pituitary. In addition, our findings suggest that basal PRL secretion by the lactotroph may be dependent on a normal function of the gonadotroph. The collected data from this and previous reports support the existence of a functional link between gonadotrophs and lactotrophs in the rat pituitary gland.

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

Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats.

Possible protective effects of the agonist [D-Trp6]LH-RH (analog of luteinizing hormone-releasing hormone in which Gly-6 is replaced by D-tryptophan) and antagonist N-Ac-[D-Phe(pCI)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group given 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist (1000 micrograms/kg of body weight per day) showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Thus, pretreatment of rats with LH-RH antagonist, by reversibly inhibiting gonadal function, protected the germinal cells of the testes against damaging effects of x-rays. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist [D-Trp6]LH-RH, liberating 25 micrograms of the agonist per day. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. In spite of pretreatment with [D-Trp6]LH-RH, testicular weights were significantly lower and LH or FSH levels were elevated in the irradiated groups as compared with nonirradiated controls. The recovery of spermatogenesis was incomplete, and there was a decrease in the number of germinal cells after 415 rads and especially after 622 rads. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist [D-Trp6]LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.

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

Antiserum to LH-RH blocks haloperidol-induced hyperprolactinemia in female rats.

We investigated the effect of blocking endogenous LH-RH, by injection of anti-LH-RH sera, on serum prolactin levels previously elevated by treatment with haloperidol for 5 days. An acute intravenous injection of rabbit anti-LH-RH serum significantly reduced serum LH levels and blocked the hyperprolactinemia induced by haloperidol. In another group of rats, sheep anti-LH-RH serum induced a significant decrease of serum LH and also lowered serum prolactin levels previously elevated by haloperidol. In ovariectomized rats, sheep anti-LH-RH serum markedly reduced serum LH levels and also decreased serum prolactin elevated by the pretreatment with haloperidol. It is concluded that the blocking of endogenous LH-RH action results in a decreased release of prolactin in response to stimuli like haloperidol. These results support the possible existence of a paracrine interaction between the pituitary gonadotrophs and lactotrophs.

Animals↗
PubMed1985

D-Trp-6-luteinizing hormone-releasing hormone inhibits hyperprolactinemia in female rats.

The effect of a potent agonistic LHRH analog D-Trp-6-LHRH on the hyperprolactinemia induced by haloperidol was tested in intact and ovariectomized female rats. The administration of D-Trp-6-LHRH at two dose levels (5 and 50 micrograms/day) for 20 days blocked the increase in serum PRL induced by haloperidol in intact as well as ovariectomized rats. The pituitary PRL concentration was also decreased by the administration of the analog in intact, but not ovariectomized, rats. Serum LH levels were significantly increased and the pituitary LH concentration was reduced by D-Trp-6-LHRH in intact rats. In ovariectomized rats, D-Trp-6-LHRH decreased serum as well as pituitary LH levels compared with levels in control rats. Another in vivo model to induce hyperprolactinemia consisted of grafting anterior pituitary glands under the kidney capsule in intact female rats. The administration of D-Trp-6-LHRH for 20 days (50 micrograms/day, sc) to rats bearing pituitary grafts blocked the hyperprolactinemia observed in similar animals injected with the vehicle only. Serum LH levels were increased after the administration of D-Trp-6-LHRH, whereas pituitary LH concentrations were significantly decreased in the rats treated with the analog. These results demonstrate that the LHRH agonist D-Trp-6-LHRH can counteract the hyperprolactinemic effect of haloperidol, and that this effect is not mediated by suppression of ovarian estrogens. The treatment with the analog blocked the hypersecretion of PRL by pituitary grafts, suggesting a direct effect of the analog on the pituitary gland to modulate PRL secretion.

Animals↗
PubMed1984

The effect of ethanol on prolactin secretion in vitro.

In order to investigate the action of ethanol on the anterior pituitary gland, the effect of ethanol on prolactin secretion in vitro was studied. Ethanol significantly increased the in vitro incorporation of 3H-leucine into both prolactin contained within the pituitary gland and that released into the medium. The enhancement of 3H labelled-prolactin synthesis induced by ethanol was suppressed by cycloheximide. These results support the hypothesis that ethanol stimulates the in vitro synthesis and release of prolactin by the pituitary gland.

Acetaldehyde↗
PubMed1983

GABA-related enzymes in the hypothalamus of rats treated with estradiol.

The possibility that the activity of GABA-related enzymes in the hypothalamus, glutamic acid decarboxylase (GAD) and GABA-transaminase (GABA-T), may be modified by circulating prolactin levels was investigated in castrated female and male rats. Estradiol benzoate was chosen to induce an increase, while bromergocriptine was used to obtain a decrease of serum prolactin levels. Acute treatment with estradiol benzoate brought about 3 h later, a significant increase of serum prolactin, and a slight, non-significant increase of GAD activity in the hypothalamus. Chronic treatment with estradiol benzoate for 12 days induced significant increases in serum prolactin and GAD activity in the hypothalamus. Bromergocriptine significantly blocked this increase of GAD activity. Bromergocriptine-treated rats had significant increases of GABA-T activity in the hypothalamus. The results of this investigation support the possibility of the existence of a relationship between GABA-related enzymes in the hypothalamus and circulating prolactin levels.

4-Aminobutyrate Transaminase↗
PubMed1983

Effect of a powerful antagonist of LH-RH on testicular function in prepubertal male rats.

The effects of N-Ac-D-p-F-Phe1,D-p-Cl-Phe2,D-Trp3,6,D-Ala10-LH-RH, a new antagonistic analog of LH-RH, were tested on the testicular function and serum FSH and LH levels in immature male rats. Prolonged administration of this analog to prepubertal male rats resulted in lower testicular and seminal vesicle weights as compared with control rats treated with the vehicle only. Spermatogenesis was markedly delayed in rats injected with the analog. Serum FSH and LH levels were significantly lower in the analog-treated rats as compared to the controls. These data show that LH-RH antagonists may be useful for inhibition of spermatogenesis.

Animals↗