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R Collu

Publications and source records attributed to R Collu.

At least 55 records · Page 3Linked to original sources
PubMed1985

Effects of chronic bromocriptine treatment of an estrone-induced, prolactin-secreting rat pituitary adenoma.

Bromocriptine (BROM), a dopamine (DA) agonist, is commonly and successfully used for long-term treatment of human prolactinomas. We have studied the effects of chronic BROM administration to female 344 Fisher/Lis rats bearing an estrone-induced, prolactin (PRL)-secreting pituitary tumor recently characterized as a model for human prolactinoma. The animals were injected twice daily with BROM (2.5 mg/kg) or with diluent. After 1 month of treatment, the animals were sacrificed, and plasma collected and stored at -20 degrees C for PRL radioimmunoassay. The pituitary tumors were removed and tumoral mammotrophs dispersed enzymatically for studies of DA receptor binding and PRL release in vitro. BROM treatment significantly reduced tumor weight, cell size, rough endoplasmic reticulum, Golgi complexes and plasma PRL levels. [3H]-spiroperidol binding to tumoral mammotrophs was also evaluated. BROM induced a significant decrease in the number of DA binding sites without any changes in affinity. These results indicate that chronic BROM treatment of an animal model of prolactinoma induces tumor involution, reduction of PRL release and probably synthesis, and down regulation of dopaminergic binding sites.

Adenoma↗
PubMed1984

Estrone-induced, prolactin-secreting and dopamine-sensitive rat pituitary tumor.

Prolactin (PRL)-secreting rat pituitary tumors were induced in female Fisher 344/Lis rats by s.c. implants of estrone (E1) pellets. Tumor growth was relatively fast and reached about 100 mg within 2 months. Ovariectomy at the time of E1 implants seemed to accelerate the growth of the tumors. Tumor cells in primary culture produced mainly PRL, while growth hormone (GH) release was about 2% of PRL production and the release of some other pituitary hormones did not exceed 1% of PRL values. Tumor cells were found to have high-affinity dopamine (DA) receptors. The addition of DA in vitro at 10(-10) M concentration stimulated PRL release, while at 10(-6) M concentration it inhibited the release of the hormone by more than 50% of control values. Histological, immunohistochemical and electron microscopical studies demonstrated the tumor to be composed mainly of maximally stimulated mammotrophs.

Animals↗
PubMed1984

Role of catecholamines in the inhibitory effect of immobilization stress on testosterone secretion in rats.

Immobilization stress applied for 6 h induced, in adult male rats, a rise of epinephrine (E) and norepinephrine (NE) plasma levels and a decrease of baseline plasma testosterone (T) values and of human chorionic gonadotropin (hCG)-induced T response. Treatment of the animals for 5 weeks with guanethidine (G), a sympathetic neuron toxic agent, significantly decreased E and NE responses to stress and partly antagonized the inhibitory effects exerted by immobilization on T biosynthesis. Adrenalectomy totally suppressed circulating E and reduced the stress-induced NE increase while partly antagonizing the inhibitory effects exerted on T biosynthesis. Combined G and adrenalectomy treatments totally suppressed plasma E and NE, and completely blocked the effects of immobilization on T levels. Treatment of the animals with the alpha 1-adrenergic blocker, prazosin, and the beta 1-adrenergic blocker, metoprolol, did not modify the effects of stress on T biosynthesis. Treatment with propranolol or with butoxamine, a nonspecific beta- and a specific beta 2-adrenergic receptor blocker, respectively, antagonized the testicular hyposensitivity to hCG induced by stress. Stress- or treatment-induced changes of plasma luteinizing hormone (LH) and hCG levels were not consistently correlated with plasma T modifications. These findings suggest that at least part of the inhibitory effects of immobilization stress on T biosynthesis is exerted by catecholamines through a beta 2-adrenergic receptor.

Adrenal Glands↗
PubMed1984

Effect of glucocorticoids on testosterone production by porcine Leydig cells in primary culture.

For this study, purified immature porcine Leydig cells in primary culture were used. After 2 days of culture, the cells were incubated with dexamethasone (5 X 10(-9), 1 X 10(-7) M) for various periods of time (3-45 h). The media were discarded and treatment was repeated with or without the addition of human chorionic gonadotropin (HCG, 10 mIU/mL) for 3 h. Dexamethasone (10(-7) M) decreased testosterone production of HCG-treated cells (up to 40%) in a time-dependent fashion while the lower dose was ineffective. The effect of varying doses (10(-8) and 10(-6) M) of natural glucocorticoids (corticosterone, cortisol) or synthetic glucocorticoids (triamcinolone, triamcinolone acetonide, betamethasone, dexamethasone) and that of a synthetic progestin (R-5020) on cultured Leydig cells was also studied. After 18 h of preincubation, the various synthetic but not the natural steroids nor R-5020, were able to decrease testosterone production of control and HCG-treated cells by 20-40%. Of a number of other hormonal and nonhormonal substances studied at concentrations of 10(-9)-10(-5) M, only lysine8-vasopressin at a concentration of 10(-6) M was able to inhibit testosterone production by these cells. These results indicate that dexamethasone and other synthetic glucocorticoids, and to a lesser degree lysine8-vasopressin, may exert a direct inhibitory effect on testosterone production by purified porcine immature Leydig cells in vitro.

Animals↗
PubMed1984

The 3 beta-hydroxysteroid dehydrogenase activity of cultured porcine Leydig cells in primary culture.

Previous studies have shown that there is a spontaneous progressive increase in human chorionic gonadotropin (HCG)-stimulated testosterone (T) production by immature porcine Leydig cells during primary culture for 3 days, whereas basal T production is unaltered. Preliminary data indicated that during this time, there was an increase in the activity of the 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). The purpose of the present study was to further characterize this increase. 3 beta-HSD was assayed by measuring the conversion of tritiated dehydroepiandrosterone (DHEA) to androstenedione in the presence of NAD+. A ninefold increase in activity occurred between days 1 and 2 and only twofold between days 2 and 3. A 5- to 20-fold increase of the apparent maximum velocity of the enzyme was observed after 3 days of culture while the apparent Km remained unchanged. Cycloheximide treatment (150 ng/mL) completely abolished this spontaneous increase in enzyme activity. In parallel experiments, the stimulatory effect of HCG on T and DHEA production was inhibited by cycloheximide treatment by 90% and 60%, respectively, whereas basal T production was not affected. These results suggest that the spontaneous increase of 3 beta-HSD activity in primary cultures of porcine Leydig cells is secondary to de novo protein synthesis and that this phenomenon may be partially responsible for the increased responsiveness of these cells to HCG during the culture period.

3-Hydroxysteroid Dehydrogenases↗
PubMed1984

Dopaminergic binding sites in human pituitary adenomas other than prolactinomas.

Binding studies of [3H]-spiroperidol, a potent dopamine antagonist, were performed on dispersed cells obtained from 2 mixed PRL- and GH-secreting adenomas, 3 GH-secreting adenomas and 4 'nonsecreting' pituitary tumors. Saturable, high affinity binding sites for [3H]-spiroperidol were identified in the two adenomas of mixed PRL and GH secretion, in 2 of 3 GH-secreting adenomas and in 2 of 4 'nonsecreting' adenomas. These data indicate that dopaminergic binding sites are present in some GH-secreting adenomas in the absence of PRL hypersecretion and in some 'nonsecreting' pituitary adenomas.

Adenoma↗
PubMed1984

Interaction of sulpiride with human pituitary dopaminergic receptors is sodium dependent.

The effects of various drugs on [3H]-spiroperidol binding to human anterior pituitary and prolactinoma membranes are studied in the presence and in the absence of sodium chloride in the incubation medium. It is shown that in the absence of NaCl, 1-sulpiride is significantly less potent in displacing the radioactive ligand from its dopaminergic binding sites than in the presence of NaCl. On the contrary, the interaction of neuroleptics (d-butaclamol and haloperidol) and dopamine agonists (apomorphine and bromocriptine) was unaffected by the NaCl conditions.

Binding, Competitive↗
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↗