Biomedical subjects

C Rivier

Publications and source records attributed to C Rivier.

At least 181 records · Page 10Linked to original sources

PubMed1986

Stress-induced inhibition of reproductive functions: role of endogenous corticotropin-releasing factor.

In the adult castrated male rat, exposure to inescapable, intermittent electroshocks inhibited the pulsatile pattern of luteinizing hormone release and markedly lowered its plasma concentrations. The central administration of the corticotropin-releasing factor (CRF) antagonist alpha-helical ovine CRF residues 9 to 41 reversed the inhibitory action of stress. Neither its peripheral injection, nor the intraventricular injection of the inactive CRF analog des-Glu to Arg ovine CRF was effective. These results suggest that endogenous CRF may mediate some deleterious effects of noxious stimuli on reproduction.

Adrenocorticotropic Hormone↗

PubMed1986

Ontogeny of the stress response in the rat: role of the pituitary and the hypothalamus.

The neonatal rat shows a period of decreased responsiveness to noxious stimuli during the first 3 weeks of life, but the nature of this impairment is still controversial. To test the functionality of the hypothalamus-pituitary-adrenal axis during this period, we studied pituitary and adrenal responsiveness to exogenous ovine CRF and the ability of various stressors (ether vapors, electroshocks, and hypoxia) to elicit ACTH and corticosterone secretion. We also measured hypothalamic CRF content and pituitary ACTH content as well as CRF-binding sites in the anterior pituitary. From days 3-10, small elevations in plasma ACTH and corticosterone levels were observed after a 3-min exposure to ether vapors or electroshocks. In contrast, during this period, a 20-min exposure to hypoxia (5% O2 in N2) was unable to trigger measurable ACTH secretion, while corticosterone was significantly elevated. From days 14-21, plasma ACTH and corticosterone levels increased significantly after exposure to ether stress, hypoxia, and, to a lesser extent, electroshocks. By contrast, administration of urethane (1.2 g/kg BW) caused a significant increase in ACTH secretion on days 3, 5, and 10, an effect that was partially suppressed by pretreatment with an anti-CRF serum. This suggests that endogenous CRF can be released by at least some stimuli as early as day 3. Direct stimulation of the pituitary with synthetic oCRF (10 micrograms/kg BW) caused significant elevations in plasma ACTH levels at all ages tested (days 3 through 21), though these increases were significantly (P less than or equal to 0.01) smaller on day 3 (2.7-fold) than on day 21 (4.3-fold). Hypothalamic CRF content as well as ACTH content increased gradually with age, but the values reached by the third week of life were still low compared to the values on day 45. Finally, anterior pituitary CRF-binding sites averaged 317 +/- 48 fmol/mg protein on day 5 and 158 +/- 22 fmol/mg protein on day 17. The affinity (Kd) of the receptor for CRF was not significantly different on day 5, 17, or 45. These results show that although pituitary corticotrophs appear to be functional at birth, exposure to stress does not elicit marked increases in plasma ACTH until day 14 of age.

Adrenal Glands↗

PubMed1986

Opioids act centrally to modulate stress-induced decrease in luteinizing hormone in the rat.

Because endogenous opioid peptides (EOP) and CRF are activated during stress and decrease LH levels when injected centrally, we have explored the roles of these peptides in the stress-induced inhibition of LH secretion. Three opioid peptide systems [i.e. endorphin (END), enkephalin, dynorphin (DYN)], are present in the hypothalamus, acting on different opiate receptor subtypes (i.e. mu, delta, kappa). We first evaluated which EOP might be involved in the stress-induced decrease of LH levels. Immunoneutralization of EOP and pharmacological blockade of opiate receptors were used to reverse the decrease in LH induced by inescapable intermittent footshock in castrated male rats. Anti-beta-END and anti-DYN-A serum (intracerebroventricularly [icv]) or pretreatment with beta-END antagonist, beta-human END-(6-31) (2 and 5 nmol, icv), or with kappa-antagonists, Mr1452 MS and Mr2266 BS (10 mg/kg BW, ip), reversed electroshock-induced decrease in LH concentrations. beta-funaltrexamine (beta-FNA), an irreversible mu 1-opiate receptor antagonist, was partially effective in blocking the inhibitory effect of stress on LH levels. Neither passive immunization with anti-enkephalin nor the pretreatment with the delta-opiate receptor antagonist, ICI 154,129, (10 and 100 nmol, icv) modified the effect of stress. We then evaluated which endogenous opioid ligands and/or receptors might mediate the inhibitory effect on LH levels of 2 nmol ovine CRF injected icv. Anti-beta-END serum and beta-human END-(6-31), reversed the CRF-induced decrease of LH concentrations, whereas beta-FNA was only partially active. Anti-DYN-A and anti-ENK serum, kappa- and delta-antagonists did not prevent the decline of LH levels in rats receiving CRF centrally. These data suggest that stress-induced inhibition of LH secretion involves the stimulation of beta-END and DYN-A systems via mu/epsilon- or kappa-opiate receptors and that the decrease in circulating LH levels induced by centrally administered CRF may be mediated by the activation of beta-END system. Therefore, it is possible that the activation of the central CRF/beta-END pathway may play an important role in the stress-induced inhibition of reproductive functions.

Animals↗

PubMed1986

beta-Endorphin modulates the inhibitory action of corticotropin-releasing factor on luteinizing hormone secretion.

The present study investigates the possible role of endogenous opioid peptides in mediating the inhibitory effect of corticotropin-releasing factor (CRF) on circulating luteinizing hormone (LH). The central injection of an antiserum against beta-endorphin (beta-END) reversed CRF-induced LH decrease in castrated male rats, while antisera raised against DYN-A or M-Enk were inactive. beta-END-(6-31) (2 nmole, icv), a beta-END antagonist, and beta-funaltrexamine (4.8 nmole, icv), a mu 1 opiate receptor antagonist, also reversed the effect of CRF on LH. Either kappa (Mr 1456 and Mr 2266) (10 mg/kg, ip), or delta (ICI 154,129) (10 nmole, icv) opiate receptor antagonists did not significantly modify the inhibitory effect of CRF on circulating LH levels. These results suggest that central beta-END participates in the inhibitory action of CRF on LH secretion.

Animals↗

PubMed1985

Effect of gonadotropin-releasing hormone antagonists on serum follicle-stimulating hormone and luteinizing hormone under conditions of singular follicle-stimulating hormone secretion.

Previous work has indicated that in long-term ovariectomized rats a potent antagonist to gonadotropin-releasing hormone (GnRH) suppressed serum luteinizing hormone (LH) more successfully than follicle-stimulating hormone (FSH). The present studies examined whether the rise in serum FSH which occurs acutely after ovariectomy, or during the proestrous secondary surge, depends on GnRH. In Experiment A, rats were ovariectomized at 0800 h of metestrus and injected with (Ac-dehydro-Pro1, pCl-D-Phe2, D-Trp3,6, NaMeLeu7)-GnRH (Antag-I) at 1200 h of the same day, or 2 or 5 days later. Antag-I blocked the LH response completely, but only partially suppressed serum FSH levels. Experiment B tested a higher dose of a more potent antagonist [( Ac-3-Pro1, pF-D-Phe2, D-Trp3,6]-GnRH; Antag-II) injected at the time of ovariectomy. The analog suppressed serum LH by 79% and FSH by 30%. Experiment C examined the effect of Antag-II on the day of proestrus on the spontaneous secondary surge of FSH, as well as on a secondary FSH surge which can be induced by exogenous LH. Antag-II, given at 1200 h proestrus, blocked ovulation and the LH surge expected at 1830 h, as well as increases in serum FSH which occur at 1830 h and at 0400 h. Exogenous LH triggered a rise in FSH in rats suppressed by Antag-II. In Experiment D proestrous rats were injected with Antag-II at 1200 h and ovariectomized at 1530 h. By 0400 h the antag had suppressed FSH in controls, but in the ovariectomized rats, a vigorous FSH response occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Differential suppression of follicle-stimulating hormone and luteinizing hormone secretion in vivo by a gonadotropin-releasing hormone antagonist.

Because of some indication that FSH secretion is less dependent than LH secretion on GnRH in vivo, we performed experiments to examine the effects of a GnRH antagonist (antag) on LH and FSH secretion. We first showed that pituitary cells superfused with GnRH showed a similar pattern of suppressed secretion of both LH and FSH in response to addition of antag. In contrast, antag administration to ovariectomized rats had differing effects on LH and FSH secretion. Serum LH was suppressed in a dose-dependent fashion by 2 h (20-50% of control values). Recovery from the lower doses of antag was seen by 12 h, but the two highest doses maintained serum LH levels at 10% of control values for 72 h. In contrast, the effect on serum FSH was not manifested until 12 h. FSH was maximally decreased only to 40-60% of control values. The two highest doses maintained this effect for 72 h. These results reinforce previous suggestions that FSH secretion in vivo may occur independently of acute changes in GnRH secretion, and may have an GnRH-independent component.

Animals↗

PubMed1985

Effect of the long-term administration of corticotropin-releasing factor on the pituitary-adrenal and pituitary-gonadal axis in the male rat.

The effect of the continuous exposure to ovine corticotropin-releasing factor (oCRF) was measured in adult male rats. The intravenous infusion of 0.75 nmol oCRF/h to intact rats over a 24-h period was accompanied by a peak of ACTH and corticosterone secretion that occurred during the first 90 min of administration of the releasing factor, followed by a decrease to lower, but still above control, values. Additionally, corticotropin-releasing factor (CRF)-treated rats had decreased plasma testosterone levels. The subcutaneous administration of 0.075 or 0.75 nmol oCRF/h to intact rats for 7 d also resulted in elevations of both plasma ACTH and corticosterone levels comparable to those measured after a 24-h exposure to the releasing factor, as well as dose-related hypertrophy of the adrenals and increases in pituitary ACTH content. In these animals, CRF markedly inhibited luteinizing hormone (LH) (but not follicle-stimulating hormone [FSH] ), testosterone, and PRL secretion and decreased seminal vesicle weights. All the effects of CRF were mimicked by exogenously administered ACTH. By contrast, with the exception of FSH secretion, which was slightly elevated by CRF, neither CRF nor ACTH were able to significantly modify reproductive parameters in adrenalectomized animals, which suggests that the elevation of circulating levels of adrenal steroids induced by peripherally administered CRF represents major mediators of CRF-induced inhibition of fertility. These results indicate that in the rat, the continuous stimulation of the pituitary-adrenal axis by peripherally administered CRF causes some degree of desensitization of the pituitary-adrenal axis, but is still accompanied by persistent elevations of the circulating levels of both ACTH and corticosteroids. The increased secretion of adrenal steroids by CRF-treated rats is believed to participate in the disruption of reproductive parameters observed in these rats.

Adrenal Glands↗

PubMed1985

Involvement of corticotropin-releasing factor and somatostatin in stress-induced inhibition of growth hormone secretion in the rat.

Corticotropin-releasing factor (CRF), which is released into the pituitary portal blood during exposure to noxious stimuli, can act centrally to inhibit GH secretion. We have investigated a possible role of endogenous CRF in mediating the stress-induced inhibition of GH release in the rat. While exposure to electroshocks markedly lowered plasma GH levels measured 20 min later, the central administration of the CRF antagonist alpha-Hel CRF-(9-41) totally abolished the effect of stress. To examine possible mechanisms through which CRF might mediate the inhibitory action of various stimuli on GH secretion, we have administered antisomatostatin (anti-SS) serum to CRF-injected rats and observed that immunoneutralization of endogenous SS blocked the inhibitory action of CRF on basal plasma GH values. Additionally, we have shown that CRF acted centrally to prevent the stimulatory action of both exogenously administered GH-releasing factor and the endogenous GH-releasing factor released by morphine sulfate. These effects were abolished by previous treatment with anti-SS serum. Such observations support the hypothesis that in the rat, endogenous CRF mediates the inhibitory action of noxious stimuli on GH secretion and further suggest that this effect may involve an increased release of endogenous SS.

Animals↗

PubMed1985

Effects of corticotropin-releasing factor, neurohypophyseal peptides, and catecholamines on pituitary function.

In freely moving rats, ovine corticotropin-releasing factor (CRF) and rat CRF, which are equipotent in stimulating adrenocorticotropin (ACTH) release, can exert this effect after either i.v. or intracerebroventricular (i.c.v.) administration. Oxytocin and epinephrine also elevate plasma ACTH levels, an effect that is abolished by immunoneutralization of endogenous CRF. Inasmuch as oxytocin and epinephrine show additivity with CRF, these results suggest that these two secretagogues stimulate ACTH secretion in vivo by interacting with endogenous CRF. Apart from its effect on ACTH release, CRF injected i.c.v. markedly inhibits luteinizing hormone (LH), but not follicle-stimulating hormone, secretion in rats in the absence of circulating levels of steroids. A similar effect is observed after i.c.v. administration of sauvagine, a peptide analogous to CRF, whereas arginine vasopressin exhibits lower potency and shorter duration of action than CRF. Because these peptides do not modify LH release by cultured pituitary cells, they probably lower plasma LH levels through centrally mediated mechanisms. These results indicate that CRF can exert a broad spectrum of action to regulate pituitary function directly or indirectly.

Adrenocorticotropic Hormone↗

PubMed1984

Synthetic competitive antagonists of corticotropin-releasing factor: effect on ACTH secretion in the rat.

Polypeptide analogs of the known members of the corticotropin-releasing factor (CRF) family were synthesized and tested in vitro and in vivo for enhanced potency or competitive antagonism. Predictive methods and physicochemical measurements had suggested an internal secondary alpha-helical conformation spanning about 25 residues for at least three members of the CRF family. Maximization of alpha-helix-forming potential by amino acid substitutions from the native known sequences (rat/human and ovine CRF, sauvagine, and carp and sucker urotensin 1) led to the synthesis of an analog that was found to be more than twice as potent as either of the parent peptides in vitro. In contrast, certain amino-terminally shortened fragments, such as alpha-helical CRF or ovine CRF residues 8 to 41, 9 to 41, and 10 to 41, were found to be competitive inhibitors in vitro. Selected antagonists were examined and also found to be active in vivo.

Adrenocorticotropic Hormone↗

PubMed1984

Differential suppression of FSH and LH secretion by follicular fluid in the presence or absence of GnRH.

The differential role of porcine follicular fluid (pFF) in regulating follicle-stimulating hormone (FSH) and luteinizing hormone (LH) release in vivo in situations of different gonadotropin releasing hormone (GnRH) backgrounds was studied. In experiment 1, 2-week ovariectomized rats injected intravenously with 4, 16 or 64 mg of protein from pFF, showed a dose-dependent suppression of FSH over time, with a maximal suppression to 40% of control values by 10 h. LH levels were slightly, but significantly, elevated by the two lower doses, but not by the highest dose of pFF. In experiment 2, 64 mg pFF was superimposed (i.v. injection) in ovariectomized rats injected subcutaneously with a high dose of GnRH antagonist (500 micrograms) 24 h earlier. The pFF suppressed FSH 35% below the level achieved in the absence of GnRH stimulation, with no effect on LH. In experiment 3, the rise in FSH secretion in acutely ovariectomized rats was shown to be inhibited by 8 or 32 mg pFF administered intravenously 3.5 h after surgery. Injection of GnRH (250 or 1,000 ng) 4.5 h after pFF could not overcome the inhibitory action of pFF on FSH, although non-pFF-treated controls responded in a dose-dependent fashion to GnRH stimulation. The expected LH response to GnRH was not affected by pFF, except in the group receiving 1,000 ng GnRH and 8 mg pFF. In these rats, LH was enhanced in one trial, but suppressed in a replicate trial, illustrating the inconsistent effects of pFF on LH under conditions of high GnRH stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Influence of corticotropin-releasing factor on reproductive functions in the rat.

The acute administration of 0.015-1.5 nmol ovine corticotropin-releasing factor (CRF) into the lateral ventricle of gonadectomized (or gonadectomized/adrenalectomized) female rats caused a rapid and prolonged dose-related inhibition of LH (but not FSH) secretion. By contrast, the acute peripheral injection of up to 15 nmol CRF was without effect in the same animal preparations. In cycling intact female rats, injection of 1.5 nmol CRF into the brain or of 75 nmol CRF sc inhibited ovulation and blocked the proestrous LH surge in about 50% of the animals. Lower doses of peripherally administered CRF were ineffective. Finally, CRF injected daily sc (15 nmol/day) to female rats during the first 12 days after mating caused a 40% disruption of pregnancy. These results indicate that CRF will lower plasma LH levels and can exert this effect in the absence of circulating steroids of either adrenal or gonadal origin. CRF inhibition of LH secretion, which we have previously reported to be absent in vitro, was unaltered by the opiate receptor antagonist naltrexone or by the ganglionic blocker chlorisondamine. Furthermore, blockade of CRF-induced beta-endorphin or ACTH release into the general circulation by dexamethasone did not interfere with the inhibitory effect of CRF on LH secretion. Such observations suggest that CRF exerts deleterious actions on reproductive functions through brain sites of action which, at least under the experimental mental design used, do not appear to directly involve opiate or peripheral catecholaminergic pathways.

Adrenalectomy↗

PubMed1984

Central nervous system regulation of adrenocorticotropin secretion: role of somatostatins.

Somatostatin-28 (SS-28) and desAA1,2,4,5,12,13[D-Trp8]somatostatin (ODT8-SS), but not somatostatin-14, given intracerebroventricularly, but not when given iv, inhibit stress-induced pituitary ACTH and adrenomedullary epinephrine secretion in rats. The elevation of ACTH after tail-suspension stress is totally prevented by iv administration of antisera raised against corticotropin-releasing factor (CRF). SS-28 and ODT8-SS do not inhibit CRF-induced ACTH secretion in vivo or in vitro. These results are consistent with the hypothesis that SS-28 and ODT8-SS prevent stress-induced ACTH secretion by inhibition of CRF release.

Adrenocorticotropic Hormone↗

PubMed1984

Multiple stimulation of the adenohypophysis by combinations of hypothalamic releasing factors.

We have investigated the in vitro and in vivo interactions of the four hypothalamic releasing factors, LHRH, corticotropin-releasing factor, TRH, and GH-releasing factor on anterior pituitary hormone secretions, using a 2 X 2 X 2 X 2 factorial experimental design. This experimental design allows for the evaluation of both the main treatment effects of the hypothalamic releasing factors as well as all of the possible interactions between them. Significant main treatment effects were: LHRH on LH and FSH, corticotropin-releasing factor on ACTH and beta-endorphin, TRH on TSH, and GH-releasing factor on GH. These results confirm the specificity of the four releasing factors on their respective target cells. There were no significant interactions between any of the releasing factors on anterior pituitary hormone secretions. These results suggest that the changes in pituitary secretion that are observed under physiological conditions are not due to interactions between the hypothalamic releasing factors at the level of the pituitary, but rather to other secondary interactions that modify pituitary activation or response. These results also indicate that the clinical pituitary reserve tests can be expanded to include all four hypothalamic releasing factors, since any lack of response will reflect a specific pituitary defect and not a failure to respond owing to interaction of the secretagogues administered.

Adrenocorticotropic Hormone↗

PubMed1984

Corticotropin-releasing factor (CRF) acts centrally to inhibit growth hormone secretion in the rat.

The intracerebroventricular administration of 0.15 and 1.5 nmol ovine corticotropin releasing factor ( oCRF ) to freely-moving adult male rats resulted in a dose-related inhibition of spontaneous GH secretion. This inhibition lasted for at least 3 h and was statistically significant at all time points. By contrast, the iv injection of 1.5 nmol oCRF was without effect. These results suggest that CRF can act within the central nervous system to interfere with spontaneous GH secretion.

Animals↗

PubMed1984

Studies of the nature of the interaction between vasopressin and corticotropin-releasing factor on adrenocorticotropin release in the rat.

Arginine-vasopressin (AVP) acts on vasoconstriction and diuresis through two different types of receptors (V1 and V2, respectively). Since AVP also modifies ACTH release, we have attempted to determine which class of receptors mediates the capacity of AVP to increase ACTH secretion and to potentiate the effect of corticotropin-releasing factor (CRF) on the pituitary using two AVP antagonists: [1-deaminopenicillamine-2-(O-methyl)tyrosine]arginine-vasopressin [dPTyr(Me)-AVP], which blocks V1 receptors, and [1-beta-mercapto-beta,beta-cyclopentamethylene propionic acid)2-D-leucine-4-valine]arginine vasopressin [d(CH2)5DLeuValAVP], which interferes with V2 receptors. dPTyr(Me)AVP, but not d(CH2)5DLeuValAVP, inhibited the ACTH-releasing as well as the CRF-potentiating effects of both AVP and its antidiuretic analog [1-deamino-8-D-arginine]vasopressin (dDAVP). These results suggest that the actions of AVP and dDAVP on the corticotrophs is primarily mediated through V1 (pressor-like) receptors.

Adrenocorticotropic Hormone↗

PubMed1984

Effect of ethanol on the hypothalamic-pituitary-adrenal axis in the rat: role of corticotropin-releasing factor (CRF).

The acute i.p. administration of alcohol (EtOH) to freely moving, nonanesthetized rats caused dose-related elevations in plasma adrenocorticotropin (ACTH) and corticosterone levels. In vivo, injection of anticorticotropin-releasing factor (CRF) serum (i.v.) totally abolished this stimulatory effect, suggesting that the induction of CRF secretion by EtOH represents an essential modulator of its ability to release ACTH. Exposure to high levels of alcohol vapors for 7 days was accompanied by a decrease in hypothalamic CRF content. The acute exposure of cultured pituitary cells to 0.2% EtOH did not modify basal or CRF-induced ACTH release, whereas pretreatment of the cells with EtOH for 24 hr resulted in a marked decrease in both spontaneous and stimulated ACTH secretion. It is therefore possible that the long-term exposure to alcohol may result in an increase of CRF release by the median eminence, as well as in some loss of pituitary responsiveness. From these data, we hypothesize that the acute EtOH-induced activation of the hypothalamic-pituitary-adrenal axis probably takes place at the level of CRF-secreting neurons and that this effect may play a role in the disturbance of ACTH and corticosteroid secretion observed during chronic exposure to alcohol.

Adrenocorticotropic Hormone↗

PubMed1983

Effect of angiotensin II on ACTH release in vivo: role of corticotropin-releasing factor.

The ability of angiotensin II (ANG II) to release ACTH was studied in vivo. ANG II elicited dose-related increases in plasma ACTH levels in freely-moving non-anesthetized rats. The observation that this effect was totally abolished by immunoneutralization of endogenous CRF, as well as the lack of stimulatory activity of ANG II in pharmacologically blocked animals, suggest that the induction of CRF secretion by ANG II represents an essential modulator of the ACTH-releasing potency of this peptide.

Adrenocorticotropic Hormone↗