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)

Pharmacological data suggest that opiates, acting indirectly via the catecholaminergic system, are involved in the inhibition of LH release and the stimulation of PRL secretion. The aim of this study was to demonstrate on the ultrastructural level whether beta-endorphin-immunoreactive fibers form synaptic contacts with hypothalamic dopaminergic neurons. Light and electron microscopic double immunostaining experiments were performed on vibratome sections prepared from the hypothalamus of acrolein-fixed female rat brains. Immunoreactivity for beta-endorphin was visualized by a dark blue to black nickel ammonium sulfate-intensified diaminobenzidine reaction, and in a consecutive immunostaining procedure, the tyrosine hydroxylase-immunoreactive dopamine cells were labeled with the brown diaminobenzidine reaction product. Under the light microscope, beta-endorphin axon terminals were found to contact dopamine cell bodies and dendrites throughout the hypothalamus. The majority of opiate target dopamine neurons were found in the periventricular area, retrochiasmatic area, and lateral part of the zona incerta. A much smaller number was observed in the dorsomedial hypothalamic nucleus and the anterior hypothalamus, and only a very few dopamine cells could be detected in contact with beta-endorphin axons in the arcuate nucleus (particularly in the posterior part where the beta-endorphin cells are located) and the medial part of the zona incerta. After light microscopic examination and color photography, the double immunostained sections were embedded for correlated electron microscopy to verify and characterize the putative synaptic connections. Electron microscopy revealed symmetric synaptic connections between beta-endorphin-immunoreactive boutons and tyrosine hydroxylase-immunopositive cell bodies and dendrites. These results together with the observation of dopamine innervation of LHRH-producing neurons and progesterone receptor-containing cells indicate that neurons of the hypothalamic dopaminergic system probably mediate opiate effects on hypophyseal hormone secretion.
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PMID:Beta-endorphin innervation of dopamine neurons in the rat hypothalamus: a light and electron microscopic double immunostaining study. 135 5

Stress-related activation of the hypothalamic-pituitary-adrenal axis (HPA) is associated with suppression of the reproductive axis. This effect has been explained by findings indicating that corticotropin-releasing hormone suppresses hypothalamic gonadotropin-releasing hormone (GnRH) secretion via an opioid peptide-mediated mechanism, and that glucocorticoids suppress both GnRH and gonadotropin secretion and inhibit testosterone and estradiol production by the testis and ovary, respectively. To evaluate whether glucocorticoids suppress the effects of estradiol on its target tissues, we examined the ability of dexamethasone to inhibit estradiol-stimulated uterine and thymic growth in ovariectomized rats. Estradiol alone, given daily for 5 days, caused dose-dependent uterine and thymic growth. Dexamethasone alone, given daily for 5 days, caused a dose-dependent decrease in body weight gain and in thymic growth. When estradiol and dexamethasone were administered simultaneously, however, body weight gain and thymic growth were also inhibited (p less than 0.05). Dexamethasone decreased estradiol-induced uterine cytosolic and nuclear estrogen receptor concentrations (E2 R0, p less than 0.05; E2nR0, respectively), but had no effect on estradiol-induced progesterone receptor concentrations (P4R0, p greater than 0.05). Levels of uterine glucocorticoid receptors were not affected by estrogen and/or dexamethasone treatment. These findings suggest that stress levels of glucocorticoids, administered over a 5-day interval, block the estradiol-stimulated growth of female sex hormone target tissues. This effect may be partially mediated by a glucocorticoid-induced decrease of the estradiol receptor concentration. Thus, another mechanism by which the HPA may influence reproductive function during stress is by a direct effect of glucocorticoids on the target tissues of sex steroids.
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PMID:Glucocorticoids inhibit estradiol-mediated uterine growth: possible role of the uterine estradiol receptor. 231 Aug 19

The effects of the progesterone antagonist RU 38486 and the progesterone agonist megestrol acetate on the growth of the estrogen-progesterone receptor-positive transplantable adrenocorticotropin (ACTH)/prolactin-secreting rat pituitary tumor 7315a were examined. RU 38486 (2.5 mg/kg/day) for 30 days significantly inhibited tumor size, tumor weight, and the plasma prolactin and ACTH concentrations, while the same dose of megestrol acetate only inhibited pituitary tumor weight. Megestrol acetate inhibited both the release and total ACTH content of the anterior pituitary gland, while RU 38486 increased both the release and the total ACTH content. Studies with ACTH secretion by cultured normal rat pituitary cells showed that megestrol acetate (1 microM) did not affect corticotropin-releasing factor (CRF)-stimulated ACTH release after 4-hr exposure, but inhibited CRF-stimulated ACTH release by 50% after 24-hr preincubation. The glucocorticoid-like effect of 1 microM megestrol acetate in this model is similar to that exerted by 10 nM dexamethasone. Acute exposure or preincubation of rat pituitary cells with RU 38486 (1 microM) did not influence CRF-stimulated ACTH release, while preincubation for 24 hr revealed a dose-dependent reversing effect of RU 38486 on dexamethasone-induced inhibition of CRF-stimulated ACTH release. In this model, 1 microM RU 38486 completely overcame the effect of 10 nM dexamethasone. Megestrol acetate and RU 38486 have inhibitory effects on the growth of the 7315a tumor. They differ both with regard to their effects on the progesterone and the glucocorticoid receptor, with megestrol acetate exerting an agonistic and RU 38486 an antagonistic action.
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PMID:Comparison of the actions of RU 38486 and megestrol acetate in the model of a transplantable adrenocorticotropin- and prolactin-secreting rat pituitary tumor. 298 81

It is now evident that hypothalamic beta-endorphin (beta EP) modulates reproductive physiology at the central level by inhibiting the function of neurons producing gonadotropin-releasing hormone (GnRH). Increasing evidence suggests that gonadal steroids, which play an important role in the long-loop negative feedback on the hypothalamus-pituitary-gonadal axis, may exert its indirect inhibitory action through modulating the production and release of hypothalamic beta EP. However, it remains unclear whether progesterone or estrogen alone or their combination is important to exert this effect. Employing long-term monolayer neonatal hypothalamic cell cultures, we reported here that whereas progesterone significantly enhanced forskolin-, N6,2'-O-dibutyryladenosine-3'5'-cyclic monophosphate [(Bu)2cAMP]-, 3-isobutyl-1-methylxanthine (IBMX)- or cholera toxin-stimulated immunoreactive (ir)-beta EP release from cultures treated daily for 4 consecutive days, the steroid alone produced little effect. This potentiation of progesterone was time-related and dose-dependent with an EC50 value of the steroid being approximately 25 nM; at this concentration the steroid increased ir-beta EP secretion about 1.6 times (P < 0.05) that induced by 5 microM forskolin alone. Similar effects were also observed for POMC mRNA levels in cultures subjected to 6 h of the above treatment regime. This potentiating effect appears specific as it can be mimicked by progestin, a progesterone receptor agonist and blocked by the progesterone receptor antagonist RU38486, but not RU28318, a mineralocorticoid receptor antagonist. Furthermore, beta-estradiol alone failed to exert a significant effect on basal, forskolin-induced or on forskolin and progesterone co-stimulated beta EP release or POMC mRNA levels in hypothalamic cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Progesterone, but not estrogen, modulates the cAMP system mediated ir-beta-endorphin secretion and POMC mRNA expression from rat hypothalamic cells in culture. 762 Aug 93

Previous studies have demonstrated antiglucocorticoid actions for the progesterone receptor antagonist RU-486. In one study, daily administration of this drug for 2 wk decreased food intake (FI) and body weight gain (delta BW) in obese, but not lean, conventionally housed 5-wk-old female Zucker rats. We recently found that 2-wk administration of RU-486 attenuated delta BW in lean but not obese 12-wk-old male Zucker rats without affecting FI. To examine the actions of RU-486 and its effects on FI and delta BW in young (5 wk old) specific-pathogen-free (SPF) male and female Zucker rats, RU-486 was administered at 30 mg.kg-1.day-1 subcutaneously for 14 days. RU-486 did not affect FI in obese or lean male or female rats. RU-486 increased adrenal weight (P < 0.05) overall and in lean female rats and modestly decreased inguinal fat weight overall and in obese female rats (P < 0.01), suggesting some antiglucocorticoid activity in these animals. However, RU-486 also decreased thymus weight by 18-31% (P < 0.0001), increased plasma glucose by 10-16 mg/dl (P < 0.002), and increased plasma insulin by 47% in obese male rats (P < 0.028), demonstrating glucocorticoid agonist actions for the drug. Plasma corticosterone (B) and adrenocorticotropic hormone (ACTH) were elevated in vehicle-treated obese female and male rats by 150-360% (P < 0.0025) and 32-38% (P < 0.05), respectively, compared with lean rats. RU-486 treatment lowered the elevated plasma B and ACTH levels in obese female and male rats (both P < 0.02 vs. vehicle), a glucocorticoid agonist effect. We conclude that in young SPF Zucker rats 1) RU-486 administration does not alter FI or delta BW, 2) RU-486 has predominately glucocorticoid agonist actions in several tissues, 3) obese animals have increased hypothalamic-pituitary-adrenal (HPA) axis activity (plasma B and ACTH), and 4) RU-486 administration suppresses the HPA axis in obese rats.
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PMID:Predominately glucocorticoid agonist actions of RU-486 in young specific-pathogen-free Zucker rats. 885 95

Administration of steroid hormones was demonstrated to modulate the sleep electroencephalogram (EEG) and sleep-associated hormonal secretion in specific ways. The present study was conducted to compare the effects of mifepristone (Mif), a mixed glucocorticoid (GR) and progesterone receptor (PR) antagonist, and megestrol acetate (Meg), a PR agonist. Nine healthy men were pretreated with either placebo or 200 mg Mif or 320 mg Meg, or a combination of both. Changes in plasma adrenocorticotropic hormone (ACTH), cortisol, and growth hormone concentrations were registered every 30 min; sleep EEG recordings were obtained continuously. Administration of Mif increased the morning plasma ACTH and cortisol surges, whereas Meg had the opposite effect. Growth hormone secretion was lowered by Mif pretreatment and enhanced by Meg. Simultaneous administration of both compounds led to largely compensated effects. The sleep EEG changes induced by Mif were a slight increase in the time awake and a delayed onset of slow-wave sleep. Meg led to a reduction of rapid-eye-movement sleep. Simultaneous administration of Mif and Meg showed a synergism in increasing time awake and shallow sleep: it therefore may be concluded that the sleep EEG effects are mediated by an interaction of GR and PR in unknown mechanisms.
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PMID:Sleep-endocrine effects of mifepristone and megestrol acetate in healthy men. 945 59

Synthetic and naturally occurring steroids exert a variety of neural effects that include modulation of nocturnal sleep. The present study focuses on the effect of progesterone receptor (PR) activation on the nocturnal sleep electroencephalogram (EEG) in male volunteers. As a PR ligand, the synthetic progesterone megestrol was used, which has the advantage over progesterone in that it is not metabolized into other steroid compounds which could cloud the progesterone-mediated effects through their own neuroactive properties. Nine healthy male volunteers were investigated in a prospective single-blind randomized study design. They received either placebo tablets or megestrol acetate dosages of 160, 320 or 480 mg at 14.00 h and 19.00 h. Blood samples were drawn half-hourly from 22.00 h until 07.00 h. After 320 mg megestrol, plasma adrenocorticotropin secretion was lower and growth hormone secretion was higher than after 160 mg and 480 mg megestrol or placebo. Similarly, the reduction in the relative amount of rapid eye movement sleep was most pronounced after 320 mg. Thus, progesterone receptor activation, as reflected by the sleep EEG and associated pituitary hormone secretion, follows a nonlinear U-shape dose dependency of a well-defined PR ligand, which may explain the unresolved inconsistencies of neuroendocrine progesterone effects to date. Moreover, employing a CV1 cell line, contransfected with a human glucocorticoid receptor expression vector and a reporter gene-based detection system for transcriptional activity, revealed that a PR agonist such as megestrol may also activate glucocorticoid receptors. This may account for some of the neuroendocrine effects of megestrol and other progestins.
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PMID:Sleep endocrine effects of megestrol acetate in healthy men. 974 90

The intention of this review is to summarize the current knowledge on the bidirectional interaction between sleep EEG and the secretion of corticotropin (ACTH) and cortisol. The administration of various hypothalamic-pituitary- adrenocortical (HPA) hormones and their antagonists exerts specific sleep-EEG changes in several species including humans. It is well documented that corticotropin releasing hormone (CRH) impairs sleep and enhances vigilance. In addition, it may promote REM sleep. Changes in the growth hormone-releasing hormone (GHRH):CRH ratio in favour of CRH appear to contribute to shallow sleep, elevated cortisol levels and blunted GH in depression and ageing. On the other hand, in women GHRH appears to exert CRH-like effects on sleep. Acute cortisol administration increases slow-wave sleep (SWS) and GH, probably due to feedback inhibition of CRH, and inhibits REM sleep. With the mixed glucocorticoid and progesterone receptor antagonist mifepriston sleep is disrupted. Subchronic administration of the glucocorticoid agonist methylprednisolone desinhibited REM sleep. A synergism of elevated CRH and cortisol activity may contribute to REM disinhibition during depression. Also ACTH and vasopressin modulate sleep specifically but their physiological role remains unclear. For example acute icv vasopressin enhances wakefulness in rats, whereas its long-term administration increases SWS in the elderly. In various studies the interaction of sleep EEG and HPA hormones has been investigated at the baseline, after manipulation of sleep-wake behaviour and after environmental changes. Most studies agree that the circadian pattern of cortisol is relatively independent from sleep and environmental influences. Some data suggest a major effect of light on cortisol secretion. Sleeping is widely associated with blunting and awakenings are linked with increases of HPA hormones.
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PMID:Sleep and the hypothalamo-pituitary-adrenocortical system. 1253 Nov 48

Food restriction is associated with a number of endocrine disturbances. We validated the experimental conditions for several house-keeping genes and determined the effects of 12 day 50% food restriction on hypothalamic and pituitary transcription of genes involved in different neuroendocrine systems, using real-time quantitative polymerase chain reaction (PCR). A total of 7 nuclear receptors and 12 neuropeptides and peptide hormones were investigated in the dorsal and ventral hypothalamus and the pituitary gland in rats. In the hypothalamus, food restriction reduced mRNA levels of estrogen receptor alpha (ERalpha), progesterone receptor, glucocorticoid receptor, thyroid hormone receptor alpha and beta, pro-opiomelanocortin (POMC), growth hormone-releasing factor (GHRF), corticotropin-releasing factor (CRF), thyrotropin-releasing factor (TRF), somatostatin, and increased that of neuropeptide Y (NPY). In the pituitary, the treatment reduced growth hormone (GH), luteinizing hormone beta (LHbeta) and thyrotropin beta, but increased ERalpha mRNA levels. The study provides a map of how food restriction affects the regulation of a number of transcripts involved in neuroendocrine control.
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PMID:Differential regulation of nuclear receptors, neuropeptides and peptide hormones in the hypothalamus and pituitary of food restricted rats. 1566 63

The increased use of hormonal therapies over the last years has led to improve the knowledge of pharmacological, biochemical and metabolic properties of several progestins and their effects in target tissues, such as the central nervous system. Progesterone and synthetic progestational agents are able to modulate the synthesis and release of several neurotransmitters and neuropeptides in response to specific physiological and pathological stimuli. While these actions may relay on differential activation of progesterone receptor or recruitment of intracellular pathways, some of the differences found between synthetic progestins may depend on the specific conversion to neuroactive steroids, such as the 3-alpha, 5-alpha reduced metabolite, allopregnanolone. This is a potent endogenous steroid that rapidly affects the excitability of neurons and glia cells through direct modulation of the GABA-A receptors activity exerting hypnotic/sedative, anxiolytic, anaesthetic and anticonvulsive properties. Estrogens increase the CNS and serum levels of allopregnanolone and the addition of certain but not all synthetic progestins determines a further increase in allopregnanolone levels, suggesting that the metabolism into this reduced product is related to the chemical structure of progestin molecule used. In addition, depending on specific progestin molecule used, different interaction are found with the estradiol-induced beta-endorphin synthesis and release, showing that diverse progestins have specific and divergent actions on the opiatergic system. These results highlight the concept that natural and synthetic progesterone receptor agonists may systematically induce different biological actions in CNS. This may have far-reaching implications for the clinical effects and related indications of each compound.
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PMID:Progesterone and progestins: effects on brain, allopregnanolone and beta-endorphin. 1705 3


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