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C Rivier

Publications and source records attributed to C Rivier.

At least 145 records · Page 8Linked to original sources
PubMed1991

Effect of recombinant inhibin on follicle-stimulating hormone secretion by the female rat: interaction with a gonadotropin-releasing hormone antagonist and estrogen.

There is considerable support for the hypothesis that one component of FSH secretion is independent of GnRH. The ability of follicular fluid preparations containing inhibin to suppress FSH release in the absence of GnRH drive has suggested that this component might be responsive to gonadal proteins. However, follicular fluid contains several proteins that either stimulate or inhibit FSH secretion, thus complicating interpretation of the results. The recent availability of recombinant human (rh) inhibin-A has allowed us to specifically investigate the effect of this protein on FSH secretion by rats whose GnRH release and/or effect was blocked by a specific antagonist, [Ac-D2Nal1,DCpa2, D3Pa13,Arg5, D5-(p-methoxyphenyl) 5-oxo-2-aminopentanoic acid16, DAla10]GnRH, or by estradiol (E2). In a first experiment, the GnRH antagonist (100 micrograms/kg, injected sc 21 h earlier) lowered plasma immunoactive FSH levels by 36%, and rh-inhibin-A (25 micrograms/kg, injected iv 6 h earlier) lowered them by 44%. The combination of both treatments decreased FSH values by 82% (P less than or equal to 0.01 vs. either compound alone). Inhibin and the antagonist also significantly (P less than or equal to 0.01) decreased FSH bioactivity. A second experiment investigated the independent or combined effects of inhibin and E2. E2 (40 micrograms/kg, injected sc at -36 and -12 h) lowered FSH levels by 53%, and inhibin (25 micrograms/kg, injected iv at -6 h) decreased FSH concentrations by 37%. Administration of both compounds produced a 63% inhibition (P less than or equal to 0.05 vs. inhibin alone; P less than or 0.01 vs. E2 alone). Finally, we studied the interaction among the GnRH antagonist, inhibin, and E2. In this protocol plasma FSH levels in rats injected with inhibin and the antagonist did not show an additional decrease after treatment with E2. These results indicate that plasma FSH levels in rats whose GnRH receptors or secretion are blocked can be further lowered by inhibin. Thus, the ability of rh-inhibin-A to interfere with FSH secretion in the ovariectomized rat appears to involve a mechanism independent of the GnRH drive.

Animals↗
PubMed1991

Effect of recombinant activin-A on gonadotropin secretion in the female rat.

Repeated injections of recombinant human (rh) activin-A over a 2- to 3-day period are reportedly needed to stimulate the in vivo secretion of FSH. In this paper we present results showing that acute treatment with rh-activin-A caused marked and dose-dependent increases in plasma FSH, but not LH, levels in adult female rats. After one injection, maximum FSH release was observed 4 h after the administration of activin, while two injections of 100 micrograms activin/kg, 5 h apart, maintained elevated FSH levels for more than 10 h in intact diestrous day 1 females. Removal of the GnRH drive by pretreatment of ovariectomized animals with the GnRH antagonist ([Ac-D2Nal1,DCpa2,D3Pal3,Arg5,D-p-methoxyphenyl) 5- oxo-2-amino-pentanoic acid6, DAla10]GnRH; 100 micrograms/kg;) or repeated injections of the GnRH agonist ([DTrp6,Pro9,NEt,NH2]GnRH; 1 microgram/h for 5 days) did not prevent the stimulatory action of activin. Concomitant treatment with rh-inhibin-A (30 micrograms/kg], on the other hand, completely blocked FSH secretion induced by 100 micrograms activin/kg. These results indicate that activin-A is a powerful stimulus for FSH secretion in the female rat and exerts this effect independently of GnRH.

Activins↗
PubMed1991

Differential regulation of corticotropin-releasing factor mRNA in rat brain regions by glucocorticoids and stress.

The regulation of corticotropin-releasing factor (CRF) mRNA expression in the rat brain by glucocorticoids and stress was examined by Northern blot analysis and in situ hybridization histochemistry. Rats either were exposed to a single electrical footshock session and killed 2, 4, 12, or 24 hr later (acute stress), or were subjected to the same regimen twice daily for 3 or 7 d and killed on the day following the last session (chronic stress). Rats placed in the experimental chamber but not administered shock comprised a "sham-handling" group. Chronic (7 d) intermittent footshock stress resulted in an 84 +/- 26% (P less than 0.05) increase in CRF mRNA levels in the whole hypothalamus as detected by Northern blot analysis and a 97 +/- 29% (P less than 0.05) increase in the paraventricular nucleus (PVN) as detected using in situ hybridization. No significant change in CRF mRNA levels was observed in the hypothalamus at any time up to 24 hr after a single exposure to footshock stress. A different pattern of results was obtained in other CRF-expressing cell groups. In Barrington's nucleus (a pontine micturition center), both acute and chronic stress produced significant increases in CRF mRNA, while in the olfactory bulb, both paradigms resulted in decreased levels. By Northern blot analysis, CRF mRNA in the olfactory bulb declined steadily, beginning at 4 hr after acute stress, and reached significance at 24 hr (69.2 +/- 1.9% of control, P less than 0.05). Levels from chronically (7 d) stressed animals declined to 54.1 +/- 5.1% of control value (P less than 0.05). Analysis of hybridization histochemical material revealed that both the number of positively hybridized cells and the number of silver grains per cell in the mitral and external plexiform layers of the bulb decreased following acute and chronic stress. However, CRF mRNA levels in the olfactory bulb were decreased to a comparable extent in the sham-handling group, suggesting that exposure to a novel environment can effect a decrease in CRF mRNA levels in the olfactory bulb. To provide comparisons with the effects of manipulation of glucocorticoid status, comparable analyses were carried out in separate groups of animals following adrenalectomy (ADX) with and without corticosteroid replacement. After ADX, CRF mRNA levels in the whole hypothalamus increased 60 +/- 5% (P less than 0.05) and were normalized following dexamethasone replacement. In contrast to the hypothalamus, no effects of steroid manipulation on CRF mRNA levels in the olfactory bulb, midbrain, cerebral cortex, or brain stem were detected.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenalectomy↗
PubMed1990

Prolonged exposure to alcohol: effect on CRF mRNA levels, and CRF- and stress-induced ACTH secretion in the rat.

We have conducted studies in intact adult male rats, designed to examine the effect of a 3- or 7-day exposure to alcohol (EtOH) on the pituitary's response to corticotropin-releasing hormone (CRF) or stress, and on CRF expression in the hypothalamus. In a first series of experiments, rats exposed to EtOH vapors for 7 days had mean blood alcohol levels (BAL) of 127 +/- 12 mg%. At the end of the 7-day period, basal plasma ACTH levels were 69 +/- 10 pg/ml in control rats and 121 +/- 23 pg/ml in EtOH animals (P less than or equal to 0.01). Resting corticosterone levels were 39 +/- 11 ng/ml in control animals, and 101 +/- 24 ng/ml in EtOH rats (P less than or equal to 0.01). In all experiments described here, there was no statistical difference (P greater than 0.05) between the body weights of controls (animals kept in chambers with normal atmosphere) and EtOH-exposed animals. In control animals, the injection of 0.3-10 micrograms ovine CRF per rat caused dose-related increases in plasma ACTH levels measured 10 min later. All doses of CRF also significantly (P less than or equal to 0.01) stimulated ACTH secretion by EtOH rats, but there was no clear dose-response curve. Though EtOH-treated animals responded to the lower dose of CRF (0.3 microgram) with larger increases in plasma ACTH levels than control rats, the only statistical difference (P less than or equal to 0.01) between control and EtOH rats was observed following administration of 10 micrograms CRF, which caused a blunted response in EtOH animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1990

Role of endotoxin and interleukin-1 in modulating ACTH, LH and sex steroid secretion.

We have shown that the endotoxin LPS acted both at the level of the brain and the gonads to stimulate the hypothalamic-pituitary-adrenal, and inhibit the hypothalamic-pituitary-gonadal, axis. Exogenously administered IL-1 mimics most of the effects of LPS on pituitary activity. In addition, antibodies against IL-1 receptors can interfere with LPS-induced ACTH secretion. These results suggest that at least part of the ability of LPS to alter endocrine functions appears to depend upon endogenous interleukin-1.

Adrenocorticotropic Hormone↗
PubMed1990

Central action of recombinant interleukin-1 to inhibit acid secretion in rats.

The influence of recombinant human interleukins-1 beta and -1 alpha and rat interleukin-1 beta on gastric acid secretion was investigated in awake rats with pylorus ligation. IC injection of either human interleukin-1 beta, human interleukin-1 alpha, or rat interleukin-1 beta induced a dose-dependent inhibition of gastric acid output. At IC doses less than 100 ng, human interleukin-1 beta was more effective than the other forms or sources of interleukin-1, whereas at higher doses (100-500 ng), human interleukins-1 beta and -1 alpha and rat interleukin-1 beta were equipotent. The inhibitory effect was observed 30 minutes after interleukin-1 injection and maintained throughout the 6-hour experimental period. IC injection of interleukin-1 beta inhibited vagally stimulated gastric acid secretion induced by IC injection of the stable thyrotropin-releasing hormone analogue RX 77368. Indomethacin (1, 5, and 10 mg/kg, IP, -30 minutes) induced a dose-related prevention of the inhibitory effect of IC interleukin-1 beta. IC injection of the corticotropin-releasing factor antagonist alpha-CRF9-41, bilateral adrenalectomy, and noradrenergic blockade with bretylium did not influence the antisecretory effect of interleukin-1. Polypeptide action was not related to changes in circulating gastrin levels. Human interleukin-1 beta injected IV also inhibited gastric acid secretion, but the peripheral dose required to induce a significant effect was 10(3)-fold higher than when given centrally. These results show that IC interleukin-1 beta acts centrally to induce a long-lasting inhibition of gastric acid secretion, and this effect requires the integrity of prostaglandin pathways. These data suggest a possible interaction between the immune and gastrointestinal systems.

Animals↗
PubMed1990

Critical role of the hypothalamic pituitary adrenal axis in amphetamine-induced sensitization of behavior.

Behavioral sensitization can be observed with repeated administration of amphetamine where the intensity of motor stimulation increases over time. The process of sensitization has been well characterized, however, the neurochemical mechanisms that are critical for the development of sensitization are not known. In the present study, the role of the hypothalamic pituitary adrenal axis (HPA) in the development of behavioral sensitization to amphetamine was explored by pretreating rats with an intravenous administration of an antiserum to corticotropin-releasing factor in a volume that has been shown to block significantly stress- and cocaine-induced activation of the HPA. Four groups of eight rats were pretreated intravenously with either heparinized saline or CRF antiserum and subcutaneously with saline or d-amphetamine in a balanced design. The rats were then returned to their home cages and left undisturbed for seven days after which they were given three consecutive behavioral tests with saline SC, 0.75 mg/kg d-amphetamine SC, and 3.0 mg/kg d-amphetamine SC. The rats pretreated with intravenous CRF antiserum showed a significant attenuation of the development of d-amphetamine-induced sensitization but the antiserum did not alter the magnitude of the behavioral response to the initial, sensitizing dose of d-amphetamine. These results suggest that activation of the hypothalamic pituitary adrenal axis may be of critical importance to the development of behavioral sensitization to amphetamine.

Animals↗
PubMed1990

Central corticotropin-releasing factor mediates the suppressive effect of stress on natural killer cytotoxicity.

CRF acts within the brain to elicit changes in neuroendocrine, autonomic, and behavioral activity similar to that observed after stress. A reduction of splenic natural killer (NK) activity has also been described after the central administration of CRF. In this study we examined whether the central release of CRF plays a physiological role in mediating stress-induced suppression of NK cytotoxicity. Four sessions of footshock stress (1.5 mamp; 1-sec duration; 60-Hz sine wave; delivered randomly twice per min for 30 min) over a 48-h period significantly (P less than 0.001) reduced splenic NK activity in the rat. Pretreatment of the animals by central administration of polyclonal CRF antibodies completely antagonized the stress-induced suppression of NK cell activity. In contrast, the peripheral immunoneutralization of CRF was ineffective. Measurement of circulating levels of ACTH and corticosterone demonstrated that stress-induced elevations of ACTH and corticosterone were significantly (P less than 0.05) attenuated by peripheral anti-CRF serum, but not by centrally administered anti-CRF. These findings suggest that endogenous brain CRF coordinates the suppressive effect of footshock stress on NK cytotoxicity independently of pituitary-adrenal activation.

Adrenocorticotropic Hormone↗
PubMed1990

Cytokines act within the brain to inhibit luteinizing hormone secretion and ovulation in the rat.

Alterations of immune activity are often accompanied by reproductive disorders. Because interleukins mediate the host's response to immune activation, we first examined the effect of the central injection of several lymphokines on LH secretion by gonadectomized rats. We then studied the ability of the most potent lymphokine in this system, interleukin-1 beta (Il-1 beta), to interfere with the proestrous LH surge and ovulation in the intact female rat as well as the dependence of this effect on the activation of opiate receptors. Finally, we investigated the possibility that increased brain levels of Ils, as induced by the central administration of a bacterial endotoxin, might also alter the normal ovulatory process. After intracerebroventricular (icv) injection, Il-1 beta, Il-6, and tumor necrosis factor all lowered plasma LH levels in castrated rats. On a molar basis, Il-1 beta was the most potent inhibitor of LH secretion. In gonadectomized animals, 2.5 and 10 ng Il-1 beta administered icv significantly (P less than or equal to 0.01) decreased plasma LH levels for 6 h, while the effect of 40 ng lasted up to 12 h. By contrast, FSH secretion was only measurably altered by 40 ng Il-1 beta 8 and 12 h posttreatment. In intact cycling female rats, icv injection of 40 ng Il-1 beta or 400 ng Il-1 alpha at 0830 h on the morning of proestrus significantly (P less than 0.01 and P less than 0.05, respectively) interfered with the proestrous surge of LH. In contrast, the peripheral administration of either lymphokine was without measurable effect. Centrally injected Il-1 beta (40 ng at 0830 h on proestrus) also blocked ovulation in most animals, while a dose of 25 ng injected iv was ineffective. Finally, we observed that the icv injection of endotoxin (a lipopolysaccharide), also interfered with ovulation. The possible involvement of opiate-dependent pathways in mediating the inhibitory action of Il-1 beta on reproductive processes was tested by implanting naloxone pellets 16-24 h before lymphokine treatment. The pellets, which released 200, 400, or 800 micrograms naloxone/h (corresponding to approximately 0.6, 1.32, or 2.64 mg/kg BW.h), had no effect on ovulation by themselves. When given before icv Il-1 beta, all naloxone regimens countered the effect of the cytokine, with the 800-micrograms/h dose restoring ovulation in eight of nine rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1989

Possible involvement of inhibin in altered follicle-stimulating hormone (FSH) secretion during dissociated luteinizing hormone (LH) and FSH release: unilateral castration and experimental cryptorchidism.

Male rats were either unilaterally or bilaterally castrated, or were rendered cryptorchid when they were either 15 or 45 days old. Subsequently, blood was sampled over the next several weeks and plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and immunoreactive inhibin-alpha (irI alpha) levels were measured by specific radioimmunoassays (RIAs). At the end of the experiment, gonadal expression of inhibin-alpha, inhibin-beta A, and inhibin-beta B subunits was measured by S1 nuclease analysis and in situ hybridization. In both age groups, bilateral castration (BC) produced the expected marked (p less than or equal to 0.01) increases in plasma LH and FSH levels, and concomitant decreases in T and irI alpha secretion within 1 - 2 days after surgery. In 15-day-old animals, unilateral castration (UC) significantly increased FSH and decreased circulating levels of irI alpha, but did not measurably alter LH or androgen production. At 7 days after surgery, the level of inhibin mRNA in the remaining testis was unchanged. In 45-day-old animals, UC caused a measurable increase in FSH, with little or no changes in the circulating levels of irI alpha. Plasma T levels were lowered (p less than or equal to 0.05) by UC; however, there were no statistical changes in LH levels in these UC rats. Finally, T administration markedly reversed UC-induced increase in FSH secretion in both age groups. Androgen therapy also interfered with inhibin release in 45-day-old, but not in 15-day-old rats. In rats 15 days old at the time of surgery, cryptorchidism produced a small but measurable increase (p less than or equal to 0.05) in LH release at Week 6 only, which was accompanied by a significant (p less than or equal to 0.01) decline in T secretion. Plasma FSH levels were elevated at all times in cryptorchid rats, and at 2, 4, and 6 wk, these levels were not statistically distinguishable (p greater than 0.05) from those of castrated animals. In this group of rats, cryptorchidism caused a transient increase (p less than or equal to 0.05) in irI alpha values 1 wk after surgery, but no changes at later times. Finally, measurement of testicular inhibin-alpha subunit messenger RNA (mRNA) levels showed an approximately 2-fold increase compared to total RNA levels in the testis. However, because of the significant decrease in total RNA levels per testis caused by cryptorchidism, the absolute change in inhibin-alpha subunit mRNA levels per testis corresponded to an approximately 3-fold decrease.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Immunoreactive inhibin secretion by the hypophysectomized female rat: demonstration of the modulating effect of gonadotropin-releasing hormone and estrogen through a direct ovarian site of action.

To investigate the possibility that sex steroids and GnRH might act directly at the level of the ovary to modulate the secretion of immunoreactive inhibin, we have administered estradiol benzoate, PMSG, or GnRH analogs to immature (24-day-old) hypophysectomized female rats. The sc injection of 10-100 micrograms estradiol benzoate markedly (P less than or equal to 0.01) increased plasma inhibin levels measured 48 h later. Administration of the GnRH agonist [DTrp6,Pro9-NEt]GnRH significantly (P less than or equal to 0.05) inhibited both spontaneous and PMSG-induced inhibin secretion, while the GnRH antagonist [Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA), DAla10]GnRH augmented the stimulatory effect of PMSG action on inhibin release. These results suggest a direct ovarian site of action of sex steroids and GnRH analogs in modulating the release of immunoreactive inhibin. They also support the hypothesis that an endogenous GnRH-like peptide of ovarian origin plays a physiological paracrine role in modulating inhibin secretion in the rat.

Animals↗
PubMed1989

Production and regulation of inhibin subunits in pituitary gonadotropes.

Two related proteins, inhibin and activin, are produced and secreted by the gonads and act at the pituitary to regulate FSH secretion. In the present study, the alpha and beta B, but not the beta A, polypeptide subunits of inhibin were localized in the cytoplasm of FSH- and LH-immunoreactive (ir) gonadotropes. Ovariectomy (OVX) increased the size and number of cells immunoreactive for inhibin-alpha and -beta B as well as the mRNAs encoding these subunits. Treatment with estrogen prevented these effects. These results suggest that pituitary gonadotropes are sources, as well as targets, of inhibin-related peptides, whose expression in the pituitary is modulated by ovarian factors.

Animals↗
PubMed1989

In the rat, interleukin-1 alpha acts at the level of the brain and the gonads to interfere with gonadotropin and sex steroid secretion.

These studies were designed to investigate a possible effect of the monokine interleukin-1 alpha (Il-1 alpha) on gonadotropins and/or sex steroid secretion. Three putative sites of action were considered: the central nervous system, the pituitary, and the gonads. A central nervous system-mediated mechanism was tested by injecting Il-1 alpha into the lateral ventricle of the brain of castrated rats; this treatment caused a dose-related inhibition of LH secretion, with a minimum effective dose below 0.1 microgram (6.6 pmol) and a maximum effect at 1 microgram (66 pmol). The plateau response was observed 120 min after injection. The possibility that Il-1 alpha might alter pituitary sensitivity was studied by administering 200 ng GnRH, iv, into gonadectomized control rats or rats pretreated with 1 micrograms Il-1 alpha intracerebroventricularly. GnRH induced a comparable increase in the plasma LH levels of both groups of animals. Finally, hypophysectomized immature (24-day-old) female rats were used to determine if we could confirm in vivo that interleukin-1 alpha can act directly at the level of the ovary to interfere with steroidogenesis. In these animals, the sc injection of 20 IU PMSG produced a marked (P less than 0.01) increase in plasma estradiol levels, while the sequential injection of 20 IU PMSG and 1 microgram hCG significantly (P less than 0.01) stimulated progesterone release. The ip administration of 1 microgram Il-1 alpha every 12 h to gonadotropin-treated rats resulted in a significant inhibition of both estradiol and progesterone secretion. The results support possible roles for Il-1 alpha at the levels of the brain and the gonads, but not the pituitary, to inhibit reproductive functions.

Animals↗
PubMed1989

Immunoneutralization of endogenous inhibin modifies hormone secretion and ovulation rate in the rat.

Studies were conducted to determine the effects of inhibin immunoneutralization on gonadotropins and sex steroids secretion, as well as ovulation rate and the outcome of pregnancy in the rat. These changes were compared to the normal pattern of hormone release during the estrous cycle, as well as to the ovulatory and gestational history of control animals. Measurement of plasma inhibin levels with antibodies raised against the N-terminus part of the alpha-chain of the molecule indicated an increase in immunoreactive inhibin-alpha release during the afternoon of proestrus, followed by a marked decline after the primary gonadotropin surge. Removal of endogenous inhibin by the iv injection of anti-inhibin serum on diestrus-1 caused the expected rise in plasma FSH, but not LH values. FSH secretion remained elevated for approximately 28 h, then returned to baseline. While not altering vaginal cytology, the injection of the antiserum during diestrus-1 or -2, and to a lesser degree, during estrus, caused a marked increase in the number of tubal ova shed during the subsequent estrus. However, plasma estrogen and progesterone remained comparable at all times between control and treated animals. In female rats mated after inhibin immunoneutralization at diestrus-1, the increase in ovulation rate resulted in a significant increase in developing fetuses, but only ca. 40% of the pups survived. In order to assess whether elevated FSH secretion represented the primary mechanism through which removal of endogenous inhibin increased the number of maturing follicles, ovine FSH was infused for 35 h starting in diestrus-1 or diestrus-2. Similar to the treatment with the anti-inhibin serum, FSH infusion caused an increase the number of eggs present in the oviducts on the next day of estrus. These results support the existence of a close functional relationship between the circulating levels of FSH and inhibin in the female rat. They also indicate that immunization against inhibin increases ovulation rate, a phenomenon probably mediated through elevated levels of circulating FSH.

Animals↗
PubMed1989

Possible role of luteinizing hormone and follicle-stimulating hormone in modulating inhibin secretion and expression during the estrous cycle of the rat.

In the female rat, plasma immunoreactive inhibin alpha (irl alpha) levels show marked changes during proestrus and estrus. We investigated the modulating effect of LH and FSH on these changes by injecting the GnRH antagonist DNal-DCpa-DPal-Dpr-(Ac)Dal-Leu-Arg-Pro-Asn-NH2, with or without exogenous LH replacement. Administration of the antagonist at noon on proestrus abolished the primary (proestrus) LH and FSH surge and markedly reduced the secondary (estrus) FSH surge. This treatment also reduced the release of irl alpha normally measured during proestrus afternoon, and partially prevented the decrease in irI alpha secretion on proestrus evening. Exogenous LH injected at 1545 h on proestrus had no measurable effect on irI alpha or FSH levels in control rats; however, in antagonist-treated animals, it restored the secondary FSH surge to control values while augmenting the late proestrus fall in irI alpha. This suggests that the decrease in inhibin secretion measured after exogenous LH treatment represents the mechanism through which LH induced the secondary FSH surge in antagonist-blocked rats. We also used in situ hybridization techniques to examine the changes in the expression of inhibin subunits in the ovary at 0200 h on estrus. The antagonist reduced expression of the alpha-, beta A-, and beta B-subunits in all follicle and tissue types, with the exception of the granulosa cells of large tertiary (possibly preovulatory) follicles where the signal appeared greatly enhanced. These changes were reversed by LH. The alteration in inhibin subunit messages caused by blockade of the primary gonadotropin surge suggests the presence of a cross-regulation between LH and inhibin/activin secretion, so that a decline in circulating LH levels might stimulate inhibin/activin secretion in the granulosa cells of preovulatory follicles, while reducing the production of these proteins in less mature follicles and in other ovarian cell types.

Animals↗