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R Collu

Publications and source records attributed to R Collu.

At least 55 records · Page 3Linked to original sources
PubMed1984

Sodium ions: their role and mechanism of action in the control of prolactin release.

The secretion of PRL by the pituitary gland is under a tonic inhibitory control exerted by dopamine. However, the mechanisms involved in this inhibition remain to be completely defined. We have investigated the effects of sodium removal in the incubation medium on baseline PRL, on the inhibitory effects exerted by bromocriptine, haloperidol and cobalt, and on the stimulatory action of TRH and vasoactive intestinal polypeptide (VIP) on PRL release by enzymatically dispersed rat anterior pituitary cells in primary culture. The effects of ouabain, tetrodotoxin, and veratridine on baseline PRL release and on the inhibitory effects of dopaminergic agents were also investigated. Basal PRL release was slightly but significantly reduced by replacing sodium by choline in the incubation medium and was almost completely suppressed when isoosmolar concentrations of glucose were substituted for sodium. On the other hand, ouabain slightly but significantly increased basal release of the hormone. In the absence of sodium, the dose-dependent inhibitory effect of bromocriptine was greatly reduced. Of two antidopaminergic drugs, haloperidol and l-sulpiride, only the first inhibited the release of PRL at high doses (10(-5) - 10(-4) M) in the presence of sodium but became stimulatory at 10(-4) M in the absence of the ion. Ouabain, tetrodotoxin, and veratridine failed to significantly modify the inhibitory effects of either dopamine or bromocriptine. The dose-dependent inhibitory effects of cobalt and the releasing actions of TRH and VIP were not significantly influence by sodium removal from the incubation medium, although VIP appeared to be active at a lower concentration in the absence of the ion. These data indicate that, although the presence of a normal ionic charge in the incubation medium is essential for the baseline secretion of PRL, sodium ions specifically play only a minor role in a phenomenon which is essentially Ca2+-dependent. They also clearly show that sodium intervenes in dopaminergic agonist and antagonist inhibition of PRL release through a mechanism which appears independent of either dopaminergic receptor, Ca2+ or Na+ channel, or Na+/K+ pump. It is hypothesized that a normal intracellular sodium concentration is essential for dopaminergic agonist or antagonist inhibitory action.

Animals↗
PubMed1984

Down-regulation by 17 beta-estradiol of D2 dopamine receptors in the MtTF4 pituitary tumor.

We have recently reported that 17 beta-estradiol (E2) paradoxically inhibits the growth of the rat MtTF4 pituitary tumor which has been induced by estrogen administration. While looking for a molecular explanation for these divergent effects, we observed that E2 treatment resulted in a marked decrease of D2 dopamine receptors (RDA) in the tumor but not in normal pituitary glands. Herein, we characterize further the effect of E2 on RDA concentration in the tumor. Three weeks after a sc injection of a MtTF4 -cell suspension, adult male Fischer rats were treated, or not, either with E2 or with various other steroids. The number of dopamine-binding sites (Bmax) was determined on crude membranes by Scatchard analyses with the dopamine antagonist [3H]spiroperidol. Only one kind of binding site was observed, and the affinity constant for [3H]spiroperidol was not significantly modified by any of the various treatments used. The decrease of Bmax after 8 days of treatment was dose dependent and was maximal with 5-micrograms daily doses of E2. With 10 micrograms E, daily, Bmax decreased exponentially with the duration of the treatment; t 1/2 was approximately 5 days. Treatment for 8 days with progesterone (50 micrograms/day), dihydrotestosterone (50 micrograms/day) or 17 alpha-estradiol (10 micrograms/day), known to be inactive on tumor growth, did not alter Bmax, whereas diethylstilbestrol (10 micrograms/day) or dexamethasone (50 micrograms/day), which inhibit tumor growth, were as efficient as E2 in decreasing Bmax. In conclusion, the number of dopamine-binding sites in the membranes of MtTF4 tumor is decreased by E2 in a time- and dose-dependent fashion. Circumstantial evidence suggests that this decrease is due to a loss of RDA per cell rather than the loss of RDA-bearing cells. The relationship between the control of dopamine-binding sites and cell growth is not clear; however, this model may be useful for the elucidation of the mechanism by which E2 modulates cell membrane properties.

Animals↗
PubMed1984

Role of arginine-vasopressin (AVP) in stress-induced inhibition of testicular steroidogenesis in normal and in AVP-deficient rats.

It has been recently demonstrated that immobilization stress induces in rats a state of testicular desensitization to gonadotropins as well as a post-cAMP blockade of testosterone (T) biosynthesis. Since arginine-vasopressin (AVP) has recently been found to antagonize in rats the in vitro T-releasing effect of human CG, with this work we have verified whether AVP might be involved in stress-induced inhibition of T biosynthesis. In Sprague-Dawley and Long-Evans adult male rats chronically cannulated in the jugular vein, a small but statistically significant rise of plasma AVP levels was observed after 2 h of immobilization stress. The iv infusion of AVP (1 micrograms/kg/h) to chronically cannulated rats induced a fall of plasma T levels. A dose-dependent inhibition of plasma T values was also observed 3 h after ip administration of AVP (1, 5, 25 micrograms/kg) in animals killed by decapitation. An antagonist of AVP pressor activity [1-(beta-mercapto-beta 1 beta-cyclopentamethylenepropionic acid), 2-(O-methyl)tyrosine] AVP, antagonized, when injected ip at a dose of 30 micrograms/kg, the T-inhibitory effects of 3 h of immobilization stress. No consistent changes in plasma LH levels were observed in these experiments. To further evaluate the role of AVP in stress-induced T inhibition, AVP-deficient Brattleboro rats were submitted to 2 or 3 h of immobilization stress concomitantly with rats of the original Long-Evans strain. After 2 h and even more after 3 h of stress, plasma T levels fell in Long-Evans rats together with basal and human CG- or cAMP-stimulated T production by Percoll purified Leydig cells. In Brattleboro rats, 2 h of stress had no effects on plasma T levels nor in vitro basal or stimulated T production, whereas 3 h of immobilization were as effective as in Long-Evans animals. These results suggest, therefore, that at least part of T inhibitory effects of immobilization, those occurring during the first 2 h of stress, are due to an AVP-induced, post-cAMP blockade of T biosynthesis. Since plasma corticosterone, during 2 h of stress, rose to similar, albeit smaller, levels in Brattleboro rats as compared to those in Long-Evans animals, this glucocorticoid does not seem to be involved in the testicular effects of stress.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Maturation of the hypothalamic--pituitary--gonadal axis in the male lamb: a review.

We have studied the activity of the hypothalamic--pituitary--gonadal (HPG) axis in the male ovine fetus and newborn lamb. Circulating levels of gonadotropins, prolactin, cortisol (F), testosterone (T), dehydroepiandrosterone sulfate and delta 4androstenedione (delta 4A) were measured in fetal plasma in the third trimester of gestation and the testicular response to hCG was studied in ovine fetuses at 95 - 141 days. Ultradian variations of LH, FSH and testosterone and the testicular response to hCG also were assessed from 1 to 28 days postnatally. The data indicate that (1) fetal plasma LH, FSH, delta 4A and T levels are low from 95 days of gestation to term, while F levels increase in the last 10 days. Postnatally, F decreases rapidly. Spontaneous T peaks may occur as early as 36 hr of life. (2) Spontaneous LH and concomitant or subsequent T secretory peaks are observed by 3 days of age. (3) hCG can induce an increase in T production by interstitial cells in vitro and can increase the T testicular content and its release in the plasma from 95 days of intrauterine life. Desensitization to hCG also can be observed throughout the last trimester of gestation. We conclude that the HPG axis of the male lamb is active ty 36 - 72 hr of postnatal life and that the steroidogenic capacity of the ovine testis is developed several weeks prenatally. Consequently, the relative quiescence of the axis prenatally and in the first 24 hr of life seems to result from relatively low LH secretion and release, related to an undefined endogenous control, together with decreased Leydig cell sensitivity and relatively low enzyme activity limiting T release.

Animals↗
PubMed1983

Studies with purified immature porcine Leydig cells in primary culture.

The steroidogenic capacity of purified immature porcine Leydig cells in culture was studied over several days. The cells were obtained by fractionating crude testicular interstitial cell suspensions on a discontinuous Percoll gradient (d = 1.037, 1.042, 1.052, 1.098 g/ml), and characterized by specific binding of 125I-human chorionic gonadotropin (hCG), testosterone (T) and cyclic adenosine 3':5'-monophosphate (cAMP) production in response to hCG, and the enzymatic determination of delta 5-3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity. The Leydig cells were recovered in a density band between 1.052-1.068 g/ml and grown in a chemically defined medium (Mather et al., 1981). In the absence of hCG, T production was low throughout the 6 days of culture. However, in response to hCG (10 mIU/ml), the cultured Leydig cells showed a progressive increase in T synthesis, which reached a maximum at Days 3-4. 8-Br-cAMP (1 mM) induced a comparable rise in T production to that obtained with hCG throughout the culture period. In contrast, 8-Br-cAMP induced a near maximal increase in dehydroepiandrosterone (DHEA) production from Day 1. This paper demonstrates that purified immature porcine Leydig cells in primary culture are a valuable model to study the ontogeny of Leydig cell function.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Postreceptorial refractoriness of prolactin release mechanisms.

While a first injection of the antidopaminergic benzamide drug, sulpiride, induced a large rise in plasma prolactin (PRL) levels in chronically cannulated adult male rats, a second injection given 2 h later was totally inactive although the pituitary content of the hormone was still 76% of the initial value. When the second injection was given 8 h after the first it was slightly effective, but when administered 24 h later it was as effective as the first. The second of two consecutive injections of haloperidol given at 2-h intervals, or an injection of morphine given 2 h after sulpiride, were incapable of inducing a release of PRL. Two hours after an injection of sulpiride, a 30-min period of immobilization stress induced a significant rise in plasma PRL levels. A significant rise in plasma PRL levels was also observed when larger doses of sulpiride were given 2 h after a first injection of the drug. Apomorphine was at least as effective an inhibitor of PRL secretion when given 2 h after sulpiride than when injected after saline. In vitro studies of dopaminergic binding sites revealed the presence, in pituitary glands of sulpiride-treated rats, of receptors not modified by the drug. These data suggest that the only plausible explanation for the ineffectiveness of the second of two consecutive injections of sulpiride is the development of a state of refractoriness of the mechanisms that subserve the release of PRL induced by suppression of the inhibitory dopaminergic tonus.

Animals↗
PubMed1983

Testicular responsiveness to hCG of the ovine fetus in the last third of gestation.

The in vivo and in vitro testicular responsiveness to hCG of hemicastrated lamb fetuses 95-99, 110-118 and 130-141 days of gestational age was studied. Basal plasma testosterone (T) levels were similar at all ages (less than 0.25 ng/ml), while the mean testicular concentrations of dehydroepiandrosterone sulfate (DHA-S), 17 alpha-hydroxyprogesterone (17-OHP) and T were higher in 95- to 99-day-fold fetuses. Plasma T levels and the concentration of T, DHA-S, 17-OHP, androstenedione (A) and cyclic adenosine 3'5'-monophosphate (cAMP) were increased by hCG in the hemicastrated animal at all ages. cAMP and T production by enriched preparations of dispersed interstitial cells from control testes was increased by hCG in all groups. In fetuses pretreated with hCG in vivo the addition of hCG in vitro failed to modify cAMP and T production. 100 micrograms of LHRH to a 130-day-old fetus increased plasma LH and T levels. From these experiments, it is suggested that the low plasma LH and T levels found throughout the last trimester of fetal life reflect a relative lack of endogenous LHRH synthesis and/or release, rather than reduced testicular steroidogenic capacity.

17-alpha-Hydroxyprogesterone↗
PubMed1982

Role of midbrain raphe nuclei in stress-, pentobarbital-, beta-endorphin-, or TRH-induced changes in plasma PRL levels of adult male rats.

Radiofrequency lesions of either the dorsal (LD) or the median (LM) raphe nuclei of male rat mesencephalon did not modify baseline levels of plasma prolactin (PRL). However, the PRL releasing effect of 30 min of immobilization stress was suppressed in LM rats and enhanced in LD rats. The PRL releasing effect of pentobarbital (PB, 50 mg/kg, IP) or of beta-endorphin (END, 15 micrograms/rat, intracerebroventricularly, ICV) also was enhanced in LD rats. TRH (10 micrograms/rat, ICV) administered concomitantly with either PB or END, antagonized the releasing effect of the former and enhanced the releasing effect of the latter in sham operated rats. Lesions of the raphe nuclei blocked the antagonizing effect of TRH, while the enhancing effect was heightened in LD rats. These results indicate that neurons originating in the raphe nuclei are not involved in the control of baseline plasma PRL levels. They indicate, furthermore, the existence of an inhibitory pathway originating in the dorsal raphe nucleus the suppression or activation of which is, at least partly, the mechanism of PB, END or TRH effects on PRL release. The PRL releasing effect of immobilization stress seems to be under a dual, mutually antagonistic control: activating through the median and inhibitory through the dorsal nucleus.

Animals↗
PubMed1982

Pubertal development: normal, precocious and delayed.

The present concepts on the neuroendocrine mechanisms which trigger pubertal development and modulate the progression towards sexual maturity have been reviewed. Essentially, puberty is presented as a continuum, the programming of which is initiated prenatally and which ends in adult life when all hormonal secretions become autoregulated. This continuum is dependent on a delicate equilibrium between CNS neurohormones (GnRH), neurotransmitters (biogenic amines), pituitary gonadotrophin (FSH, LH) secretion and the end-organ response (testis or ovary) through the activation of specific membrane receptors. The gonadal sex steroids (T, OE2) will activate specific cytoplasmic and nuclear receptors of target tissues and exert their biological action. Initially, the activity of the HPGA is manifested by nocturnal LH peaks, followed by increased gonadal secretion of T or OE2. Extremely sensitive to negative feedback by circulating androgen and/or oestrogen in prepuberty, an hypothalamic regulatory system called the gonadostat increases its threshold of sensitivity and eventually becomes autoregulated at a higher feedback level. Progressively, the hypothalamus becomes sensitive to positive feedback action of gonadal hormones, this phenomenon being important for the onset of ovulation. It is likely also that adrenal androgens play a permissive and supportive role in the onset and progression of pubertal development. Finally, full maturity is reached, with final adult height through fusion of the epiphysis, and fertility is achieved. The clinical manifestations of each developmental stage of puberty are described and abnormalities of sexual development reviewed. While over 90 per cent of cases of precocious pubertal development are idiopathic in girls, a space-occupying lesion in the hypothalamic-pituitary region is frequent in boys. Dissociated pubertal signs (premature adrenarche, pubarche, thelarche, menarche) are discussed, together with diagnosis and treatment of precocious puberty, whether it is idiopathic or occurring independently of the activation of the HPGA. In addition to delay of puberty on a constitutional basis, or related to chronic endocrine or non-endocrine diseases, the main clinical entities with gonadal insufficiency, primary (hypergonadotrophic) or secondary (hypogonadotrophic), are reviewed in boys and girls and their investigation and treatment discussed.

Adolescent↗
PubMed1982

Stress-induced testicular hyposensitivity to gonadotropin in rats. Role of the pituitary gland.

The time course of stress-induced testicular hyposensitivity to gonadotropins was studied in hypophysectomized or naloxone-treated rats exposed to various periods of immobilization. Blood was collected from a chronically indwelling intra-atrial catheter every hour for luteinizing hormone (LH) and testosterone (T) measurement. Eight hours of immobilization completely suppressed T secretion without significant effect on LH. Human chorionic gonadotropin (hCG, 5 IU/rat, i.m.) induced a marked increase in plasma T levels in normal control groups 3 h post-injection while in immobilized rats the response was completely abolished, even after only 30 min of stress. In hypophysectomized rats, as expected, plasma T levels were undetectable, but, contrary to results obtained in normal animals, hCG induced a similar increase of plasma T levels both in control and stressed rats. Immobilization stress failed to inhibit plasma T values in hypophysectomized rats pretreated for 4 days with human menopausal gonadotropin (hMG) + hCG, while it did so in similarly treated normal animals. Naloxone induced a rise of plasma LH and T levels in control rats, but did not antagonize the stress-induced fall of plasma T concentration. In all groups, steroid testicular content mimicked variations of plasma T values. In particular, in stressed animals the lack of accumulation of testicular 17-hydroxyprogesterone probably reflected a normal activity of 17-20 lyase. These results indicate that stress induces very rapidly a state of Leydig cell hyposensitivity to gonadotropins and a blockade of T biosynthesis. The causal relationship between the two effects is presently not clear but these events seem to be due to stress-induced release of an inhibitory factor of pituitary origin other that endorphin.

Adrenocorticotropic Hormone↗
PubMed1982

Biosynthesis of a putative gonadotropin receptor component by rat leydig cells: isolation of a radiolabeled acidic protein of 79,000 molecular weight by affinity chromatography.

The Leydig cells of the testis are known to possess high affinity receptors for luteinizing hormone and human chorionic gonadotropin (hCG), but no information concerning the synthesis of these receptors is available yet. In order to investigate this question, we have purified crude rat interstitial cell preparations on discontinuous Percoll gradients, and Leydig cells recovered from fractions demonstrating maximum testosterone production and hCG binding capacity were incubated for 17 h in a culture medium containing [35S]methionine. Radioactive proteins solubilized with Triton X-100 were submitted to affinity chromatography on a resin consisting of hCG covalently linked to agarose. Proteins bound to the column were analyzed by two-dimensional gel electrophoresis. Autoradiography of the gel revealed a major protein (molecular weight: 79,000; pI 4.5) whose binding to the resin could be greatly diminished by an excess of hCG. The electrophoretic properties of this protein are similar to those of previously isolated gonadotropin receptor components.

Animals↗
PubMed1981

Lack of tolerance to long-term neuroleptic treatment in dopamine tuberoinfundibular system.

The plasma prolactin (PRL) levels of 35 chronic schizophrenic patients undergoing long-term maintenance treatment with neuroleptic drugs were measured before and after either neuroleptic withdrawal or a switch to a fixed dose of chlorpromazine 900 mg/day. In both men and women there tended to be a significant correlation between the initial log plasma PRL level while on neuroleptic maintenance treatment and the dosage received converted to chlorpromazine equivalents. Neuroleptic withdrawal in ech of 19 cases was followed by a decline in PRL plasma levels. Switching to chlorpromazine 900 mg/day (16 cases) produced either increases or decreases in PRL plasma levels that were significantly correlated with the change in neuroleptic dosage converted to chlorpromazine equivalents. Thus there was no evidence of tolerance to the PRL-elevating effect of neuroleptics in these patients who had been treated for many years with neuroleptics.

Adult↗
PubMed1981

Sodium-dependent interaction of benzamides with dopamine receptors in rat and dog anterior pituitary glands.

Sulpiride and other benzamides' displacement of [3H]-spiroperidol binding to rat and dog anterior pituitary dopaminergic receptors was found to be selectively sodium dependent, while typical neuroleptic activity was not influenced by NaCl. These results indicate the existence in the anterior pituitary of a subpopulation of dopaminergic receptors with which benzamides interact.

Animals↗
PubMed1981

Circulating LH, FSH, prolactin, testosterone, delta 4-androstenedione, dehydroepiandrosterone sulfate and cortisol levels in the fetus in late gestation and in newborn male and female lambs.

Gonadotropins, prolactin (PRL), testosterone (T), delta 4-androstenedione, dehydroepiandrosterone sulfate and cortisol (F) levels were determined from 14 days before birth to term in 3 female and 3 male ovine fetuses with a chronically implanted venous catheter, and in the same animals from birth to 72 h of age. In both sexes, plasma gonadotropins and androgens were low throughout the period of study while plasma F increased with gestational age. After birth, plasma gonadotropins and PRL tended to increase progressively with time while PRL concentrations were significantly higher in female than in male lambs. F and T concentrations decreased significantly within the first 12 and 6 h of postnatal life. Higher T values were again observed at 36 h in male lambs. These data indicate that the fetal hypothalamic-pituitary-gonadal axis is relatively quiescent in the last 14 days of gestation but is activated within the first 72 h after birth.

Aging↗
PubMed1981

Perinatal activity of the hypothalamic-pituitary-gonadal axis in the lamb. III. LH, testosterone and prolactin secretory pattern in newborn lambs.

Crossbred male and female lambs from Suffolk rams and Dorset-Finnish ewes born in January and February were studied at 1, 3, 7, 21 and 28 days of age and female lambs at 14 days. Ultradian variations in plasma luteinizing hormone (LH), prolactin (PRL) and testosterone were studied at 30-min intervals during a 4-hour period. In female lambs LH secretory peaks were observed at 7 days of age the amplitude of LH peaks increasing 8-fold between 7 and 14 days and 2-fold between 21 and 28 days. The number of secretory peaks also increased with age. Ultradian variations in PRL were observed from 1 day of age, the amplitude of the PRL peaks increasing also with age. In male lambs, LH and testosterone peaks were observed at 3 days of age, the testosterone peak being preceded by or concomitant with LH peaks. The amplitude of LH peaks increased with age together with basal testosterone levels although the amplitude of testosterone peaks was unchanged. This study demonstrates pulsatile secretion of LH and PRL in lambs of both sexes and of testosterone in male lambs in the first week of postnatal life. In addition, since the ovine testis is responsive to endogenous gonadotropic stimulation at this period, it is suggested that the hypothalamic-pituitary-gonadal axis is already operative at this age. It can be concluded that the hypothalamic activity concerned with pulsatile LH and prolactin secretion is present very early in the lamb neonate.

Animals↗
PubMed1981

Perinatal activity of the hypothalamic-pituitary-gonadal axis in the lamb. IV. Testicular responsiveness to hCG from 1 through 28 days of life.

Previous studies in this laboratory have shown the existence of an early postnatal activation of the hypothalamic-pituitary-gonadal axis (HPGA) in the male lamb which was present at 2 and 4 weeks of age. In order to define more precisely the time sequence of HPGA activity, we have studied the in vivo and in vitro testicular responsiveness to human chorionic gonadotropin (hCG) of the immature lamb at 1, 3, 7, 14, 21 and 28 days of life. Plasma testosterone (T) increments (delta) after hCG were lower in 1-day-old animals than in other age groups. Testicular concentrations of T, dehydroepiandrosterone and 17-hydroxyprogesterone increased from 1 to 14 days. Testicular 17, 20 lyase activity rose significantly with age but was not influenced by hCG. hCG and dibutyryl cyclic AMP increased significantly the T production by enriched interstitial cell preparation at 1, 3, and 7 days, the greatest response being found at 7 days. hCG also increased significantly the T production at 14 days. These data suggest that the lamb testis has the capacity to respond to hCG in vivo and to various stimuli vitro from the 1st day of life and that the response reaches a plateau from 2 to 4 weeks after birth.

Androstenedione↗