Anxiety-induced failure in erectile response to intracorporeal prostaglandin-E1 in non-organic male impotence: a new diagnostic approach.
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Adrenergic alpha-Antagonists↗
Biomedical subjects
A E Calogero
Publications and source records attributed to A E Calogero.
Identification, characterization, and biological activity of endothelin receptors in human ovary.
We previously reported the expression of endothelin-1 (ET-1) in granulosa cells (GCs) of the human ovary and the presence of ET-1-like immunoreactivity in human follicular fluid obtained from women in an in vitro fertilization program. In follicular fluid, but not in plasma, the levels of ET-1-like immunoreactivity were higher in gonadotropin-stimulated vs. spontaneous cycles, suggesting hormonal regulation of follicular ET-1. To identify and characterize ET receptors in human ovary, we performed autoradiography, radioligand binding, and functional studies. Mathematical analysis of families of self- and cross-competition curves among [125I]ET-1, [125I]ET-3, and selective analogs indicates that human ovary expresses both subtypes of ET receptors, i.e. ETA and ETB receptors. However, the concentration of the ETB site was 100-fold lower than that of the ETA one. By using [125I]ET-1, we demonstrated that the density of binding sites in human ovary is not affected by the hormonal milieu (similar concentrations in normal cycling, postmenopausal, and combined oral contraceptive-treated women). In situ binding studies indicate that the majority of ETA and ETB receptors are expressed in the blood vessels of the ovary. In particular, ETA receptors are abundant in the ovulatory follicles and localized in the theca interna, in close proximity to the granulosa layer. Few GCs of the ovulatory follicle were specifically labeled. Conversely, in the rat ovary, used as a control, ETB receptors were predominantly expressed and localized in GCs. Accordingly, ETB receptors negatively regulated estrogen accumulation in rat GCs. In human granulosa-luteal cells, neither ET-1 (unselective ligand) nor ET-3 or sarafotoxin 6c (ETB ligands) affected estrogen or progesterone secretion. ET-1 was 2.5-fold more potent than noradrenaline in eliciting contraction of ovarian artery, acting through the ETA receptor. Our results indicate that in human ovary, at variance with rat ovary, the endothelin system is primarily involved in the regulation of ovarian blood flow and not steroidogenesis.
Adult↗
The biobehavioral consequences of psychogenic stress in a small, social primate (Callithrix jacchus jacchus).
The biobehavioral consequences of psychogenic stress were examined using neuroendocrine and ethological methods in a captive colony of common marmosets (Callithrix jacchus jacchus). Specifically, hypothalamic-pituitary-adrenal (HPA) axis reactivity was evaluated as a function of gender and social status in four consecutive social environments [(1) stable heterosexual pairs; (2) isolation; (3) unstable peer groups; and (4) stable peer groups], by measuring both basal plasma cortisol, adrenocorticotropic hormone (ACTH) and beta-endorphin concentrations and responsiveness of these hormones to dexamethasone, ovine corticotropin-releasing hormone (oCRH), and ACTH1-24. Socially stressful conditions, such as isolation and peer group formation, were associated with increased HPA axis function and behavioral arousal, and individual profiles were related to gender and social status. Hormonal levels prior to group formation predicted subsequent status in peer groups. Basal morning concentrations of plasma cortisol, as well as cortisol responsiveness to dexamethasone suppression, were sensitive indices of HPA axis arousal during periods of social stress. The context-dependent development of hormonal and behavioral profiles, reminiscent of depression and/or anorexia nervosa, suggests that the common marmoset may be a useful model of psychiatric hypercortisolism.
Adrenocorticotropic Hormone↗
The maternal hypothalamic-pituitary-adrenal axis in the third trimester of human pregnancy.
OBJECTIVE: The third trimester of pregnancy is characterized by a mildly hyperactive hypothalamic-pituitary-adrenal (HPA) axis, possibly driven by elevated circulating levels of corticotrophin releasing hormone (CRH) of placental origin. In-vitro studies have demonstrated that glucocorticoids and oestrogen stimulate while progesterone inhibits the expression of CRH mRNA and/or protein, suggesting that several potential interactions between the placenta and the HPA axis may exist. DESIGN AND PATIENTS: To investigate the detailed pattern of circulating immunoreactive (ir) CRH, ACTH, cortisol, oestradiol and progesterone during the third trimester of pregnancy, plasma samples were drawn serially every 30 minutes from 22 healthy pregnant women (age 32.0 +/- 1.1 years, mean +/- SE) between the 34th and 36th week of gestation. Ten women had plasma samples drawn between 0800 h and 2000 h (daytime group), and 12 between 2000 h and 0800 h (night-time group). The hormone concentrations obtained were analysed for pulsatility by the Detect program, for detection of circadian rhythmicity by comparison between the first and second 6-hour periods within each group by Student's t-test, and for time-dependent correlations by cross-correlation analysis. RESULTS: All five hormones were secreted in a pulsatile fashion. There was no apparent circadian rhythm of CRH or oestradiol secretion, whereas there was a clear circadian rhythm in plasma ACTH, cortisol and progesterone secretion, with the latter in reverse phase (P < 0.05). No significant correlations were observed between CRH and ACTH, whereas, as expected, ACTH and cortisol concentrations were strongly correlated with each other over time (r = 0.32 and 0.70 at lag time 30 minutes for the daytime and night-time groups, respectively), with ACTH leading cortisol. A weak positive correlation was observed between CRH and cortisol concentrations for the night-time group at lag time 0 minute, suggesting that the latter may have a positive effect on the former in vivo. CONCLUSIONS: These data suggest that placental CRH, although pulsatile, drives quantitatively the maternal HPA axis in the third trimester of pregnancy in a non-circadian, non-pulsatile fashion. The maternal HPA axis is probably driven in a circadian and pulsatile fashion by another major ACTH secretagogue, most likely AVP of parvocellular paraventricular nucleus origin.
Adrenocorticotropic Hormone↗
Relationship between tumour necrosis factor alpha and sex steroid concentrations in the follicular fluid of women with immunological infertility.
Experimental evidence suggests a tight relationship between cytokines and the reproductive system. Tumour necrosis factor alpha (TNF alpha), a cytokine produced by activated macrophages and mesenchymal cells, seems to participate in the control of fertility. Therefore, the present study was undertaken to evaluate the concentrations of TNF alpha in the follicular fluid of female patients with immunological infertility, as well as the possible role of this cytokine in follicular development. Concentrations of TNF alpha, 17 beta-oestradiol, progesterone, androstenedione and testosterone were measured in the follicular fluid of patients with immunological infertility and patients with a tubal factor of infertility, who served as a control group. Patients with immunological infertility had significantly higher concentrations of TNF alpha in their follicular fluid compared to the control group. In contrast, oestradiol concentrations were significantly lower in the former group. The intrafollicular concentrations of the other steroids measured did not differ significantly between the two groups. The fertilization rate of ova from follicles included in the study was significantly lower in patients with immunological infertility compared to control subjects (19.1 and 57.1% respectively). In conclusion, this study shows that patients with infertility of immunological origin have increased follicular fluid concentrations of TNF alpha and lower oestradiol concentrations. We speculate that elevated TNF alpha concentrations in the human follicle may negatively influence both ovulation-and fertilization-related events.
Adult↗
Effects of gamma-aminobutyric acid on human sperm motility and hyperactivation.
This study was undertaken to evaluate the effects of gamma-aminobutyric acid (GABA) and GABAergic agonists and antagonists on sperm kinematic parameters and hyperactivation, evaluated by a computer-assisted semen analysis (CASA) system, and intracellular cAMP content in 22 normozoospermic semen samples. Because of the possible interaction of progesterone with the GABAA receptor, we also evaluated the effects of progesterone on these parameters. GABA increased beat cross frequency, curvilinear velocity (VCL), the percentage of spermatozoa moving with an average path velocity > 10 microns/s (active) and hyperactivation, and decreased linearity and straightness. Bicuculline, a GABAA receptor antagonist, antagonized the effects of GABA on all these parameters except the percentage of active spermatozoa. Muscimol, a GABAA receptor agonist, increased VCL, the percentage of active spermatozoa, and hyperactivation by about the same extent as GABA, suggesting the involvement of the GABAA receptor. However, the GABAB receptor also seems to mediate some of the effects of GABA, because baclofen, a selective agonist for this receptor, increased significantly the percentage of active spermatozoa and hyperactivation. The effect of baclofen on this latter parameter was, however, less pronounced than that obtained with GABA or muscimol. Progesterone had the same effects as GABA on sperm kinematic parameters and hyperactivation and the simultaneous presence of both compounds was not more effective than each single one. GABA and progesterone did not have any effect on intracellular cAMP content. In conclusion, GABA modulated sperm kinematic parameters and increased hyperactivation. These effects have the same magnitude of those produced by progesterone and seem to be mediated mainly by the GABAA receptor. We speculate that GABA may be a physiological regulator of sperm function.
Baclofen↗
Adenylate-cyclase-dependent pituitary adrenocorticotropin secretion is defective in the inflammatory-disease-susceptible Lewis rat.
Susceptibility to arthritis in the Lewis rat is associated with a defect of the hypothalamic-pituitary-adrenal axis. We examined the pituitary corticotropes of both intact and dexamethasone-treated male and female inflammatory-disease-susceptible Lewis and inflammatory-disease-resistant Fischer rats. We determined adrenocorticotropin levels in the media from primary cultures of anterior pituitary cells of both strains. In other experiments we have measured intracellular cyclic adenosine monophosphate and inositol monophosphate accumulation. Cells were incubated with corticotropin-releasing hormone, arginine vasopressin, forskolin, phorbol myristate acetate, or thyrotropin-releasing hormone. Corticotropin-releasing hormone stimulated adrenocorticotropin secretion from both male and female Lewis rat pituitary cells in a concentration-dependent manner. Basal and stimulated adrenocorticotropin levels in cells from Lewis rats were lower than those measured in the incubation media of Fischer rat dispersed pituitary cells. Arginine vasopressin, as well as forskolin and phorbol myristate acetate, induced a significant release of adrenocorticotropin from pituitary cells of both strains. Incubation with corticotropin-releasing hormone did not produce a significant accumulation of intracellular cyclic adenosine monophosphate in Lewis rat dispersed pituicytes of both sexes. On the other hand, forskolin induced a significant increase of intracellular cyclic adenosine monophosphate in the same cultures. Finally, inositol monophosphate accumulation was comparable in pituitary cells from both Lewis and Fischer rats of both sexes incubated with thyrotropin-releasing hormone. Adrenocorticotropin secretion from pituitary cells of male Lewis rats treated in vivo with dexamethasone was either reduced or abolished following incubation with different secretagogues. A defect in pituitary adrenocorticotropin secretion could be among the causes of the hyporesponsiveness of the hypothalamic-pituitary-adrenal axis in the Lewis rat. Such a defect appears to be associated with dysfunction of receptor-coupled events related to adenylate cyclase.
Adenylyl Cyclases↗
Effects of early parenting on growth and development in a small primate.
We report here a study of the impact of caregiver-infant relationships on physical growth and behavioral development in a small primate, the common marmoset. Somatic growth was assessed from measurements of body weight, knee-heel length, head-tail length, head circumference, and pudendal pad width in females or testis volume in males obtained from unanesthetized monkeys. Behavioral information was gathered by focal animal samples for discrete rearing behaviors. Our data suggest that the frequency of positive parental behaviors during infancy is correlated with stature when the monkeys reach 10 and 20 wk of age. Furthermore, we found that juveniles that were mistreated by their parents during infancy were smaller in body weight, knee-heel length, and head-tail length, and they demonstrated abnormal social behavior. Finally, to address whether the apparent decreased growth observed in the young animals that had experienced negative parenting was also associated with alterations in hypothalamic-pituitary-adrenal (HPA) axis function, we examined the plasma ACTH and cortisol responses to synthetic ovine corticotropin-releasing hormone (oCRH) in these animals. We found that the incremental cortisol response to exogenous oCRH was significantly lower in the young adults that had experienced negative parenting during infancy compared with those who had nonabusive parents, indicating altered hypothalamic-pituitary-adrenal axis function in these animals. Our findings suggest that the quality of parental care influences later growth and behavior in the young marmoset.
Adrenocorticotropic Hormone↗
Effects of corticotropin-releasing hormone on ovarian estrogen production in vitro.
It is a common clinical observation that stress is accompanied by dysfunction of the hypothalamic-pituitary-ovarian axis, and there is mounting experimental evidence that CRH, the principal regulator of ACTH release and the central coordinator of the stress response, is able to suppress gonadal function by inhibiting hypothalamic GnRH release. Recently, it has been shown that immunoreactive CRH, CRH messenger RNA, and CRH receptors are also present in the ovary. This prompted us to examine the role of CRH on ovarian function. To accomplish this, we studied the effects of this neuropeptide on estrogen production and cAMP intracellular content from rat granulosa and human granulosa-luteal cells. We also evaluated the activity of the enzyme aromatase by measuring the production of tritiated water from homogenates of cultured rat granulosa cells. CRH inhibited FSH-stimulated estrogen production from rat granulosa cells in a dose-dependent fashion. The maximal effect was achieved at a concentration of 10(-8) M, which suppressed estrogen production by about 30%. Low concentrations of CRH (10(-10) M), incapable of modulating maximal estrogen production in response to FSH, provoked a right-ward shift of the estrogen dose-response curve to FSH. CRH (10(-8) M) suppressed the production of tritiated water (equivalent to estrogen production) from homogenates of rat granulosa cells incubated with a half-maximal concentration of FSH. Basal estrogen production by human granulosa-luteal cells was also inhibited by CRH at a concentration of 10(-10) M. The maximal effect was achieved with a concentration of 10(-8) M, which lowered estrogen production by 25%. The CRH receptor antagonist alpha-helical CRH-(9-41) antagonized the inhibitory effect of CRH on estrogen production from rat granulosa and human granulosa-luteal cells, whereas alone it had no effect. CRH did not have any effect on the intracellular cAMP content of rat granulosa and human granulosa-luteal cells. In conclusion, these results suggest that CRH is able to suppress estrogen production from rat and human granulosa cells in vitro. This effect seems to be linked to inhibition of aromatase activity in the rat and is independent of cAMP generation. We speculate that CRH may also interfere with hypothalamic-pituitary-gonadal axis function by acting directly at the ovarian level.
Animals↗
Interaction between prolactin and catecholamines on hypothalamic GnRH release in vitro.
Brain catecholamines have been implicated in the regulation of gonadotrophin release. It has been recently reported that noradrenaline (NA), applied within the hypothalamic paraventricular nucleus, suppresses the pulsatile release of LH in the rat through a corticotrophin-releasing hormone (CRH)-dependent mechanism. Prolactin (PRL) is also able to suppress hypothalamic GnRH release following activation of the CRH-releasing neurone. Given that PRL stimulates the release of NA from hypothalamic explants and that NA stimulates the release of hypothalamic CRH, we hypothesized that this neurotransmitter may be involved in the intrahypothalamic neuroendocrine circuit mediating the inhibitory effects of PRL on GnRH release. To test this hypothesis, we evaluated the effects of PRL on GnRH release in the presence of alpha- or beta-adrenergic receptor antagonists using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated, longitudinally halved hypothalami. As previously shown, PRL at a concentration of 100 nM inhibited basal iGnRH release by about 35%. Phentolamine, a non-selective alpha-adrenergic receptor antagonist, prazosin, an alpha 1-receptor antagonist, and yohimbine, an alpha 2-receptor antagonist, overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. In contrast, propranolol, a non-selective beta-adrenergic receptor antagonist, atenolol, a beta 1-receptor antagonist, and ICI-118,551, a beta 2-receptor antagonist, had no effect. None of these compounds had any effect on basal iGnRH release. These findings suggested that an alpha-adrenergic mechanism is involved in the suppressive effects of PRL on GnRH release. Since the activation of alpha-adrenergic receptors increases hypothalamic CRH release, we evaluated whether PRL stimulates CRH release via an alpha-adrenergic mechanism. PRL stimulated basal CRH release by about twofold and this effect was inhibited by phentolamine in a concentration-dependent fashion. In conclusion, alpha-, but not beta-, adrenergic receptors mediate the inhibitory effects of PRL on GnRH release in vitro. We speculate that, at least under these experimental conditions, PRL inhibits GnRH release through an alpha-adrenergic mechanism which activates the CRH-secreting neurone.
Adrenergic alpha-Antagonists↗
The kappa-opioid receptor agonist MR-2034 stimulates the rat hypothalamic-pituitary-adrenal axis: studies in vivo and in vitro.
There is increasing evidence that opiates not only have analgesic properties, but also regulate mechanisms activated during the stress response, such as the hypothalamic-pituitary-adrenal (HPA) axis. Indeed, opioid-containing neurons innervate the paraventricular nucleus and the median eminence, thus modulating inputs to ACTH-controlling neurons. In addition, dynorphin (the endogenous ligand of the kappa-opioid receptor)-like peptides have been found co-localized with corticotrophin-releasing hormone (CRH) and are believed to be co-secreted with it in the hypophyseal portal circulation to modulate ACTH release. In this study, we evaluated the effects of the selective kappa-opioid receptor agonist MR-2034 [(-)-N-(2-tetrahydrofurfuryl)-normetazocine] on the HPA axis in vivo and in vitro. MR-2034 was given intravenously to catheterized, freely moving, male Sprague-Dawley rats and serial blood samples were collected for ACTH and corticosterone (B) measurements. We evaluated also the site of MR-2034 action on the HPA axis in vivo, after the administration of alpha-helical CRH9-41, a CRH receptor antagonist, on hypothalamic CRH, pituitary ACTH, and B release in vitro. MR-2034 increased plasma ACTH and B levels in a dose-related fashion and this effect was antagonized by the selective kappa-opioid receptor antagonist MR-1452. In the presence of alpha-helical CRH9-41, the responses of plasma ACTH and B to MR-2034 were blunted significantly, suggesting that this compound activates the HPA axis through a CRH-dependent mechanism. Accordingly, MR-2034 stimulated hypothalamic CRH release in vitro in a concentration-dependent fashion and this effect was antagonized dose-dependently by MR-1452. However, the stimulatory effect of MR-2034 on plasma ACTH and B in vivo was not completely abolished by alpha-helical CRH9-41, suggesting that an additional, CRH-independent, mechanism was involved. Indeed, MR-2034 was able to stimulate basal ACTH output in a dose-dependent manner and this effect was antagonized by MR-1452 in vitro. On the other hand, MR-2034 did not have any effect on B release from adrenocortical cells or adrenal quarters in vitro. These results show that the benzomorphan MR-2034 stimulates the HPA axis in the rat by acting at the hypothalamic and the pituitary level. We hypothesize that endogenous kappa-opioid peptides not only act at the pituitary level to increase ACTH output, but may also act at the hypothalamic level to increase CRH release through an autocrine and/or ultrashort positive feedback mechanism.
Adrenocorticotropic Hormone↗
Neurotransmitter regulation of the hypothalamic corticotropin-releasing hormone neuron.
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Acetylcholine↗
Measurements of hormonal peptides in the bronchoalveolar fluid as tumor markers of lung cancer.
A large number of lung cancers contains and releases a variety of neuropeptides such as adrenocorticotropic hormone (ACTH) and beta-endorphin (beta-EP). Although the plasma levels of these peptides have been extensively investigated as possible markers that may help in the early diagnosis of the disease, the data collected have shown their limited clinical usefulness. The present study was undertaken to evaluate whether corticotropin-releasing hormone (CRH), ACTH or beta-EP levels in the bronchoalveolar lavage (BAL) fluid of patients with lung cancer might have been more helpful. To accomplish this, bronchial lavages were carried out in 25 patients affected by lung cancer (17 squamous carcinomas, 4 adenocarcinomas, 2 small cell carcinomas, and 2 not classified) and 18 controls. After centrifugation, BAL fluid was extracted using cartridges of SepPak C-18 and CRH, ACTH and beta-EP levels were measured by radioimmunoassay. CRH and ACTH BAL levels in patients with lung cancer were not significantly different from those of controls. beta-EP concentrations in the BAL fluid were about 200-fold higher than those of ACTH and showed a downward trend (p = 0.08, Mann-Whitney test) in patients with cancer. No histologic tumor type was associated with particularly elevated levels of any of the peptides measured, not even the two patients with small cell carcinoma, a tumor type which tends to release higher peptide levels. Therefore we conclude that measurements of CRH, ACTH and/or beta-EP in the BAL fluid are not useful diagnostic tumor markers of lung cancer.
Adrenocorticotropic Hormone↗
Clinical and endocrine effects of finasteride, a 5 alpha-reductase inhibitor, in women with idiopathic hirsutism.
OBJECTIVE: To evaluate the effects of long-term administration of finasteride on hirsutism score, basal gonadotropin, and androgen secretion in women with idiopathic hirsutism. DESIGN: Randomized single-blinded study. PATIENTS: Eighteen patients with moderate-severe hirsutism were recruited for the study. INTERVENTIONS: Nine hirsute patients received 7.5 mg/d oral finasteride for a period of 9 months whereas the other nine were treated with placebo. Hirsutism score, serum basal gonadotropin, androgens, estrogen, and sex hormone-binding globulin (SHBG) levels were evaluated in all patients before treatment and every 3 months during treatment. RESULTS: After 6 and 9 months of treatment, the hirsutism score improved significantly in the patients receiving finasteride, whereas no significant modifications were observed in patients treated with placebo. The side effects observed were headache and depression of modest entity during the 1st month of treatments, whereas libido did not change. Serum levels of LH, FSH, androstenedione, unbound T, DHEAS, E2, 17 alpha-hydroxyprogesterone, and SHBG did not change during therapy. Hirsute patients treated with finasteride exhibited a marked decrease of dihydrotestosterone and a significant increase of T serum levels from the 3rd and 6th months of treatment, respectively. CONCLUSION: Finasteride decreased the hirsutism score of patients affected by idiopathic hirsutism with few side effects during treatment. No modification of libido was observed.
5-alpha Reductase Inhibitors↗
Role for serotonin3 receptors in the control of adrenocorticotropic hormone release from rat pituitary cell cultures.
Although several serotonin (5-HT) receptor types have been shown capable of stimulating the release of adrenocorticotropic hormone (ACTH) from the pituitary gland, relatively little is known about the role of the 5-HT3 receptor, a receptor that has generated a great deal of interest for its involvement in many behavioral and therapeutic effects. Hence, in this study, we tested the effects of the 5-HT3/4 receptor antagonist 3-tropanyl-indole-3-carboxylate (ICS 205-930) and the selective 5-HT3 receptor antagonist 3-tropanyl-3, 5-dichlorobenzoate (MDL 72222) on ACTH release stimulated by 5-HT from primary cultures of rat pituitary cells. Subsequently, we evaluated the effects of the selective 5-HT3 receptor agonist 1-(m-chlorophenyl)-biguanide (m-CPBG) on basal, corticotropin-releasing hormone (CRH)- and arginine vasopressin (AVP)-stimulated ACTH release. The maximal stimulatory effect of 5-HT (10(-9) mol/l) on ACTH release was antagonized by both ICS 205-930 and MDL 72222, suggesting that 5-HT stimulates basal ACTH release through activation of 5-HT3, receptors. Accordingly, m-CPBG stimulated basal ACTH release in a concentration-dependent fashion. In contrast to 5-HT, m-CPBG did not have any effect on CRH-stimulated ACTH release and inhibited AVP-stimulated ACTH release in a concentration-dependent manner. These data suggest that the 5-HT3 receptor is involved in the release of ACTH from the pituitary gland in vitro.
Adrenocorticotropic Hormone↗
Involvement of corticotropin-releasing hormone and endogenous opioid peptides in prolactin-suppressed gonadotropin-releasing hormone release in vitro.
Corticotropin-releasing hormone (CRH) has been shown capable of inhibiting hypothalamic gonadotropin-releasing hormone (GnRH) release through activation of an endogenous opioid peptide (EOP)-dependent mechanism. Recently, we have shown that prolactin (PRL) stimulates CRH release and inhibits GnRH release by hypothalami explanted from male rats. Thus, the present study was undertaken to investigate whether the inhibitory effect of PRL on GnRH release in vitro is mediated by CRH and/or EOP. To this aim, the release of GnRH in response to PRL was evaluated in presence of CRH9-41 alpha-helical (CRH-9-41), a CRH receptor antagonist, and/or naloxone (NAL), a nonselective opioid receptor antagonist, using a static hypothalamic organ culture system which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated longitudinally halved hypothalamic. As previously shown, PRL at the concentration of 100 nmol/l inhibited basal iGnRH release by about 35%. CRH9-41 or NAL overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. The simultaneous co-incubation with both antagonists was not more effective than each single antagonist. CRH9-41 did not have any effect on basal iGnRH release whereas NAL, as previously reported, increased it. In addition, PRL at the concentration of 100 nmol/l stimulated basal hypothalamic beta-endorphin (beta-EP) release. In conclusion, these data show that antagonism to CRH receptors counteracts the suppressive effects of PRL upon GnRH release and that PRL is able to stimulate hypothalamic beta-EP release in vitro.
Animals↗
Male Fischer 344/N rats show a progressive central impairment of the hypothalamic-pituitary-adrenal axis with advancing age.
We investigated the effects of aging on the regulation of hypothalamic-pituitary-adrenal function and hippocampal steroid receptors in a series of in vivo and in vitro studies conducted in healthy intact 2-, 8-, 18-, and 24-month-old male Fischer 344/N rats. Basal plasma ACTH levels were similar among age groups, and basal plasma corticosterone levels showed a significant aging-associated decline. Two i.v. doses (2 and 20 micrograms/kg BW) of rat CRF elicited significantly greater and delayed ACTH and greater corticosterone responses in older rats, consistent with the pattern encountered in hypothalamic CRF deficiency. In contrast, the i.v. injection of a muscarinic agonist, arecoline, elicited similar ACTH and corticosterone responses in all age groups. An i.v. injection of ACTH-(1-24) evoked lower corticosterone responses in the older (18- and 24-month-old) than in the younger (2- and 8-month-old) groups of rats, consistent with an impairment of hypothalamic-pituitary-adrenal axis function in older animals. Steady state mRNA levels of mineralocorticoid and glucocorticoid receptors were significantly decreased in the hippocampus of the 8-, 18-, and 24-month-old rats, compatible with maturational, rather than senescent, changes. CRF mRNA levels in the paraventricular nucleus of the hypothalamus, CRF content, and in vitro secretion by whole explanted hypothalami were progressively and significantly reduced with age, whereas the steady state levels of arginine vasopressin mRNA were significantly increased with age. Steady state levels of POMC mRNA were decreased, and ACTH content and in vitro secretion by corticotrophs were increased with age in the anterior pituitary. We conclude that male Fischer 344/N rats show a progressive hypothalamic CRH deficiency with advancing age, which appears to be associated with elevated production of arginine vasopressin in the hypothalamus.
Adrenocorticotropic Hormone↗
Effects of endothelin-1 and endothelin-3 on rat hypothalamic corticotrophin-releasing hormone and pituitary ACTH release in vitro.
Endothelins (ETs) are potent vasoconstrictor peptides that also participate in the regulation of endocrine function. Indeed, immunoreactive ET, ET mRNA and ET receptors have been found in the brain and the pituitary gland and ETs stimulate arginine vasopressin, LH, FSH, TSH and gonadotrophin-releasing hormone and inhibit prolactin release in vitro. The present study was undertaken to evaluate the effects of ET-1 and ET-3, two members of this family, on corticotrophin-releasing hormone (CRH) release by explanted male rat hypothalami in vitro and on ACTH release by primary pituitary cell culture. ET-3 decreased basal CRH release in a concentration-related manner. The lowest effective concentration tested was 3 nmol/l but a more pronounced inhibitory effect was obtained at a concentration of 10 nmol/l. On the other hand, ET-1 did not have any detectable effect on basal CRH release. Neither ET-1 nor ET-3 had any effect on the release of CRH stimulated by potassium chloride. ET-1 increased basal ACTH release, whereas ET-3 did not have any effect. Both ET-1 and ET-3 suppressed the release of ACTH stimulated by 1 nmol CRH/l. These data suggest that both ET-1 and ET-3 are able to modulate the hypothalamic-pituitary-adrenal axis function in vitro. However, they act at different levels and seem to have opposite effects. Indeed, while ET-1 stimulated pituitary ACTH release, ET-3, the peptide produced mainly in the brain, inhibited hypothalamic CRH release in vitro.
Adrenocorticotropic Hormone↗