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)

Luteinizing hormone is the major regulator of Leydig cell differentiation and steroidogenic function. A number of hormones produced by the Leydig cell (e.g. estrogen, angiotensin, CRF, vasopressin) and the tubular compartment (inhibin, TGF beta), can influence both acute and long-term actions of LH. Conversely, hormones produced in the Leydig cells modulate tubular function (e.g. androgen, beta-endorphin, oxytocin). The LH stimulatory event can be negatively influenced by the action of angiotensin II through the guanyl nucleotide inhibitory unit of adenylate cyclase. We have recently discovered an action of corticotrophin releasing hormone through specific high-affinity low-capacity receptors in the Leydig cells which involves a pertussis toxin insensitive guanyl nucleotide regulatory unit with interaction between signalling pathways and resulting inhibition of LH induced cAMP generation and consequently of steroidogenesis. In contrast to other tissues the CRF receptor in the Leydig cells did not couple to Gs. CRF action is exerted through direct or indirect action of protein kinase C, at the level of the catalytic subunit of adenylate cyclase. Physiological increases in endogenous LH cause positive regulation of membrane receptors and steroidogenesis, while major elevations in circulating gonadotropin can induce down-regulation of LH receptors and desensitization of steroid responses in the adult cell. Gonadotropin-induced desensitization in adult rat tests include an estrogen mediated steroidogenic lesion of the microsomal enzymes 17 alpha-hydroxylase/17,20-desmolase. For further understanding of the regulation of this key enzyme of the androgen pathway the rat P450(17) alpha cDNA was cloned and sequenced. This cDNA expressed in COS-1 cells 17 alpha-hydroxylase/17,20-desmolase activities. From the deduced amino acid sequence, two transmembrane regions were identified, a signal peptide for insertion in the ER, and a 2nd transmembrane region separated from the first by 122 amino acids. The carboxy terminal non-transmembrane region possesses 4 hydrophobic clefts, of which cleft II would contain the putative steroid binding site for both hydroxylase and lyase activities. The rat cDNA was employed to evaluate the hormonal regulation of mRNA levels in adult and fetal Leydig cells. Low dose hCG treatment caused an early increase in mRNA levels followed by a return to control values at later times, while with higher desensitizing doses the initial increase in mRNA was followed by a marked reduction in mRNA at 24 h and a small recovery at 48 h. Fetal rat Leydig cells treated with E2 showed a 70% decrease in P450 mRNA levels, and testosterone production closely followed the changes in mRNA.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:LH action in the Leydig cell: modulation by angiotensin II and corticotropin releasing hormone, and regulation of P450(17) alpha mRNA. 269 45

Acute changes associated with removal of the inhibition of estrus caused by suckling were examined in beef cows. Calves were weaned during the fifth week after parturition and cows were slaughtered at 0 (n = 8), 36 (n = 8) or 72 h (n = 8) after calf removal. Tissues of preoptic area (POA), hypothalamus (HYP), pituitary stalk-median eminence (SME) and pituitary neurointermediate lobe (NIL) were obtained for analyses of luteinizing hormone-releasing hormone (LHRH) and four opioid neuropeptides. In addition, one-half of each SME was superfused in vitro for measurement of basal and potassium-induced release of LHRH. The following opioid neuropeptides were quantified: methionine-enkephalin (Met-Enk), beta-endorphin (beta-EP), dynorphin-A, 1-17 (DYN-17) and dynorphin-A, 1-8 (DYN-8). All four opioid neuropeptides were most concentrated in the pituitary NIL. Luteinizing hormone-releasing hormone was most concentrated in the SME tissue, which also contained substantial concentrations of Met-Enk and beta-EP, but very little DYN-17 or DYN-8. In addition, weaning increased the weight of NIL between 0 and 36 h (P less than .05), and the concentrations of LHRH, Met-Enk, and DYN-17 in the combined POA + HYP (P less than .05) tissue between 36 and 72 h. No differences occurred among groups in SME content of LHRH or in vitro release of LHRH from the superfused SME. Although they were not affected by weaning, within-cow correlations among parameters revealed that: 1) concentrations of DYN-17 and DYN-8 were always positively correlated (P less than .05); 2) concentrations of LHRH were positively correlated with Met-Enk (P less than .01), beta-EP (P less than .05) and DYN-17 (P less than .05) in the combined POA + HYP tissue; 3) LHRH concentrations in SME tissue were negatively related to POA + HYP concentrations of Met-Enk (P less than .01) and beta-EP (P less than .05), but not of LHRH or DYN-17 and 4) in vitro release of LHRH from the pituitary SME was correlated with concentrations of DYN-8 in various tissues including the SME (P less than .01). In summary, bovine neural tissues differ widely in concentrations of the four opioid neuropeptides with NIL tissue having the greatest concentrations. Weaning calves at 36 and 72 h before slaughter caused parallel changes in LHRH, Met-Enk and DYN-17 in preoptic and hypothalamic tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relationships among concentrations of four opioid neuropeptides and luteinizing hormone-releasing hormone in neural tissues of beef cows following early weaning. 287 Oct 5

To determine the prevalence of the attenuated form of congenital adrenal hyperplasia (CAH) and hyperprolactinemia (HPPN) relative to polycystic ovarian disease (PCOD), 100 consecutive women presenting with the classic clinical features of PCOD were evaluated by basal hormonal profiles and subsequent adrenocorticotropic hormone (ACTH) stimulation tests. The study also sought biochemical markers for CAH other than ACTH stimulation. The prevalences were found to be as follows: PCOD, 65%; PCOD with HPPN, 9%; HPPN, 3%, end-organ hypersensitivity (EOH), 4%; homozygotic CAH, 4%; and heterozygotic CAH, 15%. Other than the differential response to ACTH, the only other biochemical markers observed for homozygotic CAH were significantly higher basal levels of testosterone (T) and 17 alpha-hydroxyprogesterone (17-OHP). Luteinizing hormone/follicle-stimulating hormone ratio, androstenedione, and dehydroepiandrosterone sulfate all showed no significant differences between homozygotic CAH, heterozygotic CAH, HPPN, PCOD, and EOH. This study establishes the relative prevalences of the syndromes commonly mimicking PCOD. We also conclude that the observed low incidence of CAH does not justify routine ACTH testing on all patients presenting with features of PCOD--however, our data suggest that patients with basal serum levels of T and 17-OHP greater than 50% above the upper limit of normal should undergo this dynamic test, especially if there are also certain clinical features suggestive of CAH.
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PMID:Prevalence of and markers for the attenuated form of congenital adrenal hyperplasia and hyperprolactinemia masquerading as polycystic ovarian disease. 301 93

Endopeptidase-24.11, an ectoenzyme with a key role in metabolizing peptides at cell surfaces, is present in the adenohypophysis. A specific polyclonal antibody to the endopeptidase has been used to explore its localization in cryostat sections of pig pituitary glands by an immunoperoxidase method. Immunoreactivity was symmetrically but not uniformly distributed over the anterior lobe, with the highest intensity a zone just beneath the capsule along the anterior surface. In detail, the staining was observed to be in the cell membrane, but in some cells a small area of intense paranuclear staining was also observed. Serial 5 micron sections were immunostained alternately for endopeptidase-24.11 and for pituitary proteohormone. Luteinizing hormone (LH), follicular stimulating hormone (FSH), thyrotropin, adrenocorticotropin, prolactin and growth hormone were studied in this way. It was possible to identify groups of cells in adjacent sections and a good correlation was observed for endopeptidase-24.11-immunoreactivity with that for LH and FSH. The association of the endopeptidase with gonadotrophs was confirmed by double labelling. No evidence of colocalization was observed with the other proteohormone antibodies. We conclude that among the cells of the adenohypophysis only the gonadotrophs express endopeptidase-24.11 and discuss the possible significance of this observation in regard to the termination of peptide signals, such as that of luteinizing hormone-releasing hormone (LHRH) acting at this site.
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PMID:Endopeptidase-24.11 in the adenohypophysis of the pig is localized in the gonadotrophic cells. 316 48

Luteinizing hormones-releasing hormone (LHRH), vasopressin, and corticotropin systems were examined by immunocytochemical methods in male rats 2 to 20 days after deafferentation of the basal hypothalamus. Axonal degeneration of the vasopressin system (whose perikarya lie rostral to the island) and the corticotropin system (whose perikarya lie within the island) was examined and compared with the response of the LHRH system. Vasopressin immunoreactive staining was absent in the internal zone of the median eminence 10 and 20 days after deafferentation. Disruption of the efferent projections of the opiocortin system caused the loss of almost all fiber staining outside the island by the 5th postoperative day. LHRH staining in the median eminence was modestly reduced in 5 days, considerably reduced in 10 days and negligible 20 days after deafferentation. At 10 and/or 20 days after deafferentation densely stained fibers of all three systems were observed on both sides of the cut. Invasive vasopressinergic fibers reached the lateral median eminence by the 20th postoperative day. This study reports on the response of three neuropeptide systems after complete deafferentation and demonstrates that regeneration can occur across the knife cut.
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PMID:Immunocytochemistry of luteinizing hormone-releasing hormone, vasopressin, and corticotropin following deafferentation of the basal hypothalamus of the male rat brain. 626

Hormone production in the human feto-placental unit has been studied extensively yet relatively little is known about the regulatory mechanisms involved. A tissue culture approach has been used to examine the effect of potential controlling factors on steroid production by the human mid-term fetal adrenal and mid-term and term placenta. Adrenal. The pituitary peptides corticotropin (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) had the most significant influence on adrenal steroidogenesis in both the fetal and definitive zones. Their effects were not identical: they enhanced dehydroepiandrosterone sulphate (DHA-S) production in a comparable manner but alpha-MSH had much less of a stimulatory effect on cortisol biosynthesis. Medium from homologous fetal pituitary cultures mimicked the effects of alpha-MSH rather than ACTH. Homologous placental culture medium and progesterone enhanced only cortisol production and only in the fetal zone cells. These results demonstrate that specific fetal pituitary and placental factors influence fetal adrenal activity and suggest a functional zonation of the fetal adrenal. Placenta. DHA, DHA-S and 16-hydroxy-DHA stimulated oestrogen biosynthesis while high concentrations of DHA and DHA-S (but not 16-hydroxy-DHA) inhibited progesterone production. Luteinizing hormone-releasing hormone (LRH) inhibited both oestrogen and progesterone biosynthesis. Placental steroidogenesis can therefore be influenced not only by the fetus, through its increasing adrenal output of oestrogen precursors, but also by factors originating within the placenta itself.
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PMID:Regulation of hormone production in the human feto-placental unit. 627 68

When administered to ovariectomized females, primed with oestradiol benzoate (OB) and progesterone, alpha-MSH increased lordosis behaviour in those rats that showed a low level of receptivity but in rats that were receptive it had an inhibitory effect. alpha-Melanocyte stimulating hormone also inhibited proceptive behaviour in these females. Luteinizing hormone releasing hormone (LHRH), on the other hand, failed to have a similar inhibiting effect although it did stimulate lordosis. While adrenalectomy failed to alter the stimulatory effect of alpha-MSH on lordosis it completely prevented the inhibitory actions of alpha-MSH on both lordosis and proceptive behaviour. Thus, while alpha-MSH may stimulate lordosis through a central action its inhibitory effects on lordosis and proceptive behaviour are probably mediated via the adrenal glands. Although alpha-MSH may stimulate the secretion of an adrenal steroid that blocks the facilitatory action of progesterone on female sexual behaviour the present results suggest that this inhibitory effect could be mediated by a catecholamine.
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PMID:Melanocyte stimulating hormone and the inhibition of sexual behaviour in the female rat. 635 83

We have attempted to clarify the physiological involvement of endogenous opiates in the steroid-mediated control of gonadotrophin release. Our studies showed that there was an acute reduction in the inhibitory effects of endogenous opiates on LH and FSH release following gonadectomy in the rat. This was indicated by a significant reduction in the ability of naloxone to stimulate serum LH/FSH levels (sampled at 15 min) in 26-day-old female rats 48 h after ovariectomy. Luteinizing hormone was highly sensitive to the inhibitory effects of the synthetic met-enkephalin analogue, FK 33-824, at this time (sampled at 90 min). An unexpected observation was that long-term absence of gonadal steroids also disrupted the ability of exogenous opiates, FK 33-824 and morphine, to influence LH release. This was seen as an inability of FK 33-824 (1.0 or 3.0 mg/kg) to inhibit LH secretion. The effects of gonadectomy on opiate control of LH occurred at all developmental stages and were not due to a disruption of sexual maturation. Opiate involvement in prolactin secretion did not appear to be adversely affected by an absence of gonadal steroids. Another novel aspect of this work was that the opiatergic component in the control of gonadotrophin secretion could be reinstated in long-term gonadectomized rats by treatment with oestradiol benzoate or testosterone propionate. Similarly, priming with increasing dosages of oestradiol benzoate which resulted in progressively lower LH levels gave larger naloxone in progressively lower LH levels gave larger naloxone responses.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The inhibitory effect of opiates on gonadotrophin secretion is dependent upon gonadal steroids. 643 Oct 46

A few examples of hypothalamic, peptidergic disorders leading to clinical signs and symptoms are presented in this review. Increased activity of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) and decreased activity of the vasopressin neurons in the biological clock and of the thyroxine-releasing hormone (TRH) neurons in the PVN contribute to the signs and symptoms of depression. In men, the central nucleus of the bed nucleus of the stria terminalis (BSTc) is about twice as large and contains twice as many somatostatin neurons as in women. In transsexuals this sex difference is reversed, pointing to a role of this structure in gender. Luteinizing hormone-releasing hormone (LHRH) neurons are formed in the fetal olfactory placade and migrate along the terminal nerve fibers into the hypothalamus. In Kallmann's syndrome the migration process of the LHRH (gonadotropin-releasing hormone) neurons is aborted, which explains the joint occurrence of hypogonadotropic hypogonadism and anosmia in this syndrome. In postmenopausal women, the neurons of the infundibular nucleus hypertrophy and become hyperactive because of the disappearance of the estrogen feedback and contain hyperactive peptidergic neurons. Climacteric flushes may be caused by hyperactivity of the neurokinin-B or LHRH neurons in this nucleus. The hypocretin (orexin) neurons in the perifornical area are involved in sleep. In narcolepsy with cataplexy, a loss of these neurons, probably due to an autoimmune process, is found. Obese subjects with a mutation in the gene that encodes for leptin, the preproghrelin gene, or the alpha-melanocyte-stimulating hormone (alpha-MSH) gene have been described. Decreased numbers and activity of the oxytocin neurons in the PVN may be responsible for the absence of satiety in Prader-Willi syndrome. Moreover, a glucocorticoid receptor polymorphism is associated with obesitas and dysregulation of the hypothalamus-pituitary-adrenal axis. In contrast, two single nucleotide polymorphisms (SNPs) of the AGRP gene have been associated with anorexia nervosa.
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PMID:Neuropeptides in hypothalamic neuronal disorders. 1554 16

Morphological plasticity has been demonstrated between breeding and anestrous seasons in the ewe hypothalamus, particularly for the gonadotropin-releasing hormone (GnRH) system. We sought to determine the impact of a photoperiodic transition, from long days (LD, 16 h light/24 h) to short days (SD; 8 h light/24 h), on the association between a marker of cerebral plasticity, the polysialylated form of neural cell adhesion molecule (PSA-NCAM), and two diencephalic populations: the GnRH and beta-endorphin (beta-END) neurons, the latter being potent inhibitors of GnRH neuronal activity. We also estimated the number of contacts on GnRH neurons after the passage to SD, using synaptophysin as a marker for synaptic buttons. Those parameters were evaluated in ovariectomized estradiol-replaced ewes using double immunocytochemistry and confocal microscopy at different times after the transition to SD: day 0 (D0), D30, D45, D60 and D112. Luteinizing hormone (LH) secretion was recorded throughout the experiment. High LH levels were observed only at D112. Significantly more PSA-NCAM was found in the GnRH neuron perimeters in the D112 group than in the other groups. This increase was not associated with any change in the number of synaptophysin-immunoreactive contacts on GnRH neurons. The beta-END peri-neuronal space was affected negatively by the transition to SD: the percentage of PSA-NCAM on beta-END neurons decreased between D45 and D112 in the posterior two thirds of the arcuate nucleus (ARC). These results suggest that photoperiod may reorganize cell interactions in different hypothalamic areas, ultimately reactivating GnRH neurons, in our model of ovariectomized-estradiol replaced ewes.
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PMID:Relationship between polysialylated neural cell adhesion molecule and beta-endorphin- or gonadotropin releasing hormone-containing neurons during activation of the gonadotrope axis in short daylength in the ewe. 2058 Sep 21


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