Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma 16 beta-hydroxydehydroepiandrosterone (16 beta-OH-DHEA) levels were measured by radioimmunoassay in normal and pathological conditions in man. 16 beta-OH-DHEA levels in normal subjects rose sharply during adolescence and then declined slowly throughout adult life: 192 pg/ml age 7-11, 395 pg/ml age 15-19, 330 pg/ml age 20-39, 261 pg/ml age 40-59, and 124 pg/ml over 60-years-old. No marked difference was seen between male and female subjects. 16 beta OH-DHEA rose significantly (p less than .01) during adrenocorticotropin (ACTH) stimulation, declined (p less than .005) during dexamethasome suppression and during gonadal suppression, rose (p less than .05) during gonadal stimulation and following administration of WIN 24540, an inhibitor of 3 beta-o1-dehydrogenase (p less than .005). 16 beta-OH-DHEA levels in adrenal venous blood were higher than in inferior vena cava blood but the levels in hepatic venous blood were not higher than in arterial blood. These results indicate that 16 beta-OH-DHEA is secreted directly by the adrenal cortex and probably the gonads. 16 beta-OH-DHEA levels were elevated in normal pregnant women, pregnant women with toxemia and in patients with Cushing's disease, ectopic ACTH-producing tumor and congenital adrenal hyperplasia but not in patients with low-renin essential hypertension.
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PMID:Plasma 16 beta-hydroxydehydroepiandrosterone in normal and pathological conditions in man. 18 75

The effects of inhibitors of pregnenolone metabolism, WIN-24540 and spironolactone, on adrenocorticotropic hormone (ACTH)- and human chorionic gonadotropin (hCG)-induced cAMP and steroid production by bovine (BAC) and ovine (OAC) adrenal cells and pig Leydig cells (PLC) were investigated. The inhibitors reduced cAMP production by adrenal and Leydig cells by about 75% and 60%, respectively (P less than 0.001). Further, the inhibitors also reduced the cholera toxin- and forskolin-induced cAMP production by pig Leydig cells. In the presence of the inhibitors, corticosterone and testosterone production by BAC and PLC, respectively, following hormonal stimulation was reduced by more than 90%. However, pregnenolone production by BAC and PLC under these conditions represented only 12% and 42% of the corticosterone and testosterone production, respectively, in the absence of inhibitors. Moreover, the inhibitors also reduced the steroidogenic response of PLC to 8-Br-cAMP and the conversion of 22(R)-hydroxycholesterol to pregnenolone by BAC and PLC. The reduced production of pregnenolone in the presence of inhibitors was in part due to the weak inhibition of 17 alpha-hydroxylase by spironolactone. However, when OAC cells were incubated in the presence of WIN-24540 and SU-10603, a potent 17 alpha-hydroxylase inhibitor, the amount of pregnenolone produced in response to ACTH or 22(R)-hydroxycholesterol was only 10% and 19%, respectively, of the steroids (corticosterone plus cortisol) secreted in the absence of inhibitors. The results show that the inhibitors of pregnenolone metabolism reduced, in both adrenal and Leydig cells, the response of adenylate cyclase to several effectors and the activity of the cholesterol side-chain cleavage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of hormonal-induced cAMP and steroid production by inhibitors of pregnenolone metabolism in adrenal and Leydig cells. 285 Sep 48

Exogenous cannabinoids affect multiple hormonal systems including the hypothalamo-pituitary-adrenocortical (HPA) axis. These data suggest that endogenous cannabinoids are also involved in the HPA control; however, the mechanisms underlying this control are poorly understood. We assessed the role of endogenous cannabinoids in the regulation of the HPA-axis by studying CB1 receptor knockout (KO) and wild type (WT) mice. Basal and novelty stress-induced plasma levels of adrenocorticotropin (ACTH) and corticosterone were higher in CB1-KO than in WT mice. We investigated the involvement of the pituitary in the hormonal effects of CB1 gene disruption by studying the in vitro release of ACTH from anterior pituitary fragments using a perifusion system. Both the basal and corticotropin releasing hormone (CRH)-induced ACTH secretion were similar in CB1-KO and WT mice. The synthetic glucocorticoid, dexamethasone suppressed the CRH-induced ACTH secretion in both genotypes; thus, the negative feedback of ACTH secretion was not affected by CB1 gene disruption. The cannabinoid agonist, WIN 55,212-2 had no effects on basal and CRH-stimulated ACTH secretion by anterior pituitary slices. In our hands, the disruption of the CB1 gene lead to HPA axis hyperactivity, but the pituitary seems not to be involved in this effect. Our data are consistent with the assumption that endogenous cannabinoids inhibit the HPA-axis via centrally located CB1 receptors, however the understanding of the exact underlying mechanism needs further investigation.
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PMID:The role of endogenous cannabinoids in the hypothalamo-pituitary-adrenal axis regulation: in vivo and in vitro studies in CB1 receptor knockout mice. 1545 46

Cannabinoids regulate biological processes governed by the hypothalamus including, but not limited to, energy homeostasis and reproduction. The present study sought to determine whether cannabinoids modulate A-type K(+) currents (I(A)) in neurons of the hypothalamic arcuate nucleus (ARC). Whole cell patch-clamp recordings were performed in slices through the ARC prepared from castrated female and male guinea pigs. Forty percent of guinea pig ARC neurons exhibited a transient outward current that was antagonized by high (mM) concentrations of 4-aminopyridine and (100 nM) rHeteropodatoxin-2. Five of these neurons also were immunopositive for both beta-endorphin and the Kv4.2 channel subunit. Bath application of the CB1 receptor agonists WIN 55,212-2 (1 microM) or ACEA (1 microM) selectively induced a rightward shift in the inactivation curve for the I(A), significantly increasing the half-maximal voltage without affecting the peak current magnitude, in neurons from female but not male animals. The CB1 receptor antagonist AM251 (1 microM) reversed this action. Collectively, these data reveal that guinea pig ARC neurons, including proopiomelanocortin neurons, express a prominent I(A) that is positively modulated by cannabinoids in a sex-specific way by altering the voltage dependence of its inactivation. The resultant inhibitory effect on this neuronal population may shed some insight into the mechanism(s) by which cannabinoids influence hypothalamic function.
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PMID:Sex differences in the cannabinoid modulation of an A-type K+ current in neurons of the mammalian hypothalamus. 1590 56

We sought to determine whether sex differences exist for the cannabinoid modulation of appetite, body temperature and neurotransmission at pro-opiomelanocortin (POMC) synapses. Gonadectomized male and female guinea pigs were outfitted to monitor core body temperature and injected with either the CB1 receptor agonist WIN 55,212-2 (1 mg/kg s.c.), antagonist AM251 (3 mg/kg s.c.) or vehicle (1 ml/kg s.c.) and evaluated for changes in six indices of feeding behavior under ad libitum conditions for 7 days. WIN 55,212-2 elicited an overt, sexually differentiated hyperphagia in which males displayed larger increases in hourly and daily intake, consumption/gram body weight, meal size and meal duration. The agonist also produced a more robust acute hypothermia in males than in females. In addition, males were more sensitive to the hypophagic effect of AM251, manifested by comparatively sizeable decreases in hourly intake, consumption/gram body weight, meal frequency and hyperthermia. To gain additional insight into the cellular mechanism underlying cannabinoid regulation of energy homeostasis, we performed whole-cell patch clamp recordings in hypothalamic slices prepared from gonadectomized male and female guinea pigs, and monitored miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) in arcuate (ARC) neurons. ARC neurons from females exhibited a higher basal mEPSC frequency. WIN 55,212-2 dose-dependently reduced mEPSC and mIPSC frequency; however, cells from males were far less sensitive to the CB1 receptor-mediated decrease in mIPSC frequency. These effects were observed in neurons subsequently identified as POMC neurons. These data reveal pronounced sex differences in how cannabinoids influence the hypothalamic control of homeostasis.
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PMID:Sex differences in the cannabinoid modulation of appetite, body temperature and neurotransmission at POMC synapses. 1913 14

Within the hypothalamic arcuate nucleus, two neuronal subpopulations play particularly important roles in energy balance; neurones expressing neuropeptide Y (NPY), agouti-related peptide (AgRP) and GABA are orexigenic, whereas neurones expressing pro-opiomelanocortin and CART are anorexigenic. The pivotal role of these neuropeptides in energy homeostasis is well-known, although GABA may also be an important signal because targeted knockout of the GABA transporter in NPY/AgRP/GABA neurones results in a lean, obesity-resistant phenotype. In the present study, we describe an in vitro model of K(+)-evoked GABA release from the hypothalamus and determine the effects of cannabinoid receptor activation. K(+)-evoked GABA release was sensitive to leptin, insulin and PYY(3-36), indicating that GABA was released by arcuate NPY/AgRP/GABA neurones. In the presence of tetrodotoxin (TTX), the cannabinoid CB1 receptor agonist WIN 55,212-2 inhibited K(+)-evoked GABA release. This was prevented by the CB1 receptor inverse agonist rimonabant. Rimonabant had no effect when applied alone. In the absence of TTX, however, the opposite effects were observed: WIN 55,212-2 had no effect while rimonabant inhibited GABA release. This indicates that GABA release can involve an indirect, TTX-sensitive mechanism. The most parsimonious explanation for the inhibition of GABA release by a CB receptor inverse agonist is via the disinhibition of an cannabinoid-sensitive inhibitory input onto GABAergic neurones. One local source of an inhibitory neurotransmitter is the opioidergic arcuate neurones. In our in vitro model, K(+)-evoked GABA release was inhibited by the endogenous opioid peptide beta-endorphin in a naloxone-sensitive manner. The inhibitory effect of rimonabant was also prevented by naloxone and a kappa-opioid receptor selective antagonist, suggesting that GABA release from arcuate NPY/AgRP/GABA neurones can be inhibited by endogenous opioid peptides, and that the release of opioid peptides is sensitive to cannabinoids.
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PMID:Direct and indirect effects of cannabinoids on in vitro GABA release in the rat arcuate nucleus. 2023 27