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)

Availability of recombinant growth hormone (GH) and development of long-acting formulations of this material will undoubtedly lead to widespread use of GH in animal industry and in medicine. GH can act, directly or indirectly, on multiple targets, but its influence on the reproductive system and on the hormonal control of reproduction is poorly understood. Overexpression of GH genes in transgenic animals provides a unique opportunity to study the effects of long-term GH excess. Transgenic mice overexpressing bovine, ovine, or rat GH (hormones with actions closely resembling, if not identical to, those of endogenous [mouse] GH), exhibit enhancement of growth, increased adult body size, and reduced life-span as well as a number of endocrine and reproductive abnormalities. Ectopic overexpression of bovine GH (bGH) driven by metallothionein or phosphoenolpyruvate carboxykinase promoters is associated with altered activity of hypothalamic neurons which produce somatostatin, loss of adenohypophyseal GH releasing hormone (GHRH) receptors, and suppression of endogenous (mouse) GH release. Elevation of plasma levels of GH (primarily bGH) and insulin-like growth factor (IGF-I) in these transgenic mice leads to increases in the number of hepatic GH and prolactin (PRL) receptors, in the serum levels of GH-binding protein (GHBP), in the percent of GHBP complexed with GH, and in the circulating insulin levels. In addition, plasma adrenocorticotropic hormone (ACTH) and corticosterone levels are elevated. Plasma levels of luteinizing hormone (LH), as well as its synthesis and release, are not consistently affected, but follicle-stimulating hormone (FSH) levels are suppressed, apparently due to pre- and post-translational effects. Pituitary lactotrophs exhibit characteristics of chronic enhancement of secretory activity, and plasma PRL levels are elevated. Prolactin responses to mating or to pharmacological blockade of dopamine synthesis are abnormal. Reproductive life span and efficiency are reduced in both sexes, with the severity and frequency of reproductive deficits being related to plasma bGH levels. Most transgenic females expressing high levels of bGH are sterile due to luteal failure. Overexpression of human GH which, in the mouse, interacts with both GH and PRL receptors leads to additional endocrine and reproductive abnormalities including stimulation of LH beta mRNA levels and LH secretion, loss of responsiveness to testosterone feedback, overstimulation of mammary glands, enhanced mammary tumorigenesis, and hypertrophy of accessory reproductive glands in males.
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PMID:Neuroendocrine and reproductive consequences of overexpression of growth hormone in transgenic mice. 807 44

The authors have reviewed the results of transsphenoidal surgery for pituitary adenomas done on 66 children (younger than 16 yr of age) between 1966 and 1992. Ninety-four percent (62 of 66) showed clinical evidence of pituitary hormonal hypersecretion. The most common type was the adrenocorticotropic hormone-secreting adenoma (n = 36), followed by the prolactinoma (n = 18) and the growth hormone-secreting types (n = 8). There were four cases of nonfunctioning adenomas. Adrenocorticotropic hormone-secreting tumors in children had presentations and surgical results similar to those seen in adults. Twenty-three of 33 patients with Cushing's disease had simple adenomectomy or subtotal hypophysectomy without symptomatic recurrence. Four of 10 initial treatment failures had subsequent successful surgical intervention, resulting in an overall cure rate of 78%. Postoperative hypocortisolism was suggestive of surgical success but was not absolute. Of three patients with Nelson syndrome, none were successfully treated with surgery alone and two developed invasive disease. Prolactin-secreting and growth hormone-secreting tumors in children occurred more commonly with suprasellar expansion than did their adult counterparts. Transsphenoidal surgery was capable of controlling disease in only 12% (1 of 8) of growth hormone-secreting tumors, and 67% (12 of 18) of prolactin-secreting tumors required postoperative medical therapy or radiotherapy for persistently elevated prolactin levels. Special difficulty was noted in boys with prolactinomas and in girls with primary amenorrhea. As in adults, preoperative prolactin levels correlated with ultimate surgical success rates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transsphenoidal surgery for pituitary adenomas in children. 817 79

Adenohypophysial cell types and neurohypophysial tissues were investigated in the cobalt variant of the rainbow trout, which possesses an irregularly-shaped pituitary. The pituitary remnant was completely detached from the hypothalamus in all but one fish, in which a remnant was associated with the hypothalamus. Prolactin (PRL) and growth hormone (GH) cells were predominant cell types in all pituitary remnants, forming PRL and GH areas, respectively. There were fewer somatolactin (SL) and melanophore-stimulating hormone cells than in normal fish. There were few corticotropin cells in cobalt and normal trout. Although aldehyde-fuchsin positive cells were also present, positively-staining fibers were not detected in any of remnants examined. Plasma SL levels were much lower in cobalt than in normal trout. Plasma levels of GH and T3 were significantly lower in cobalt than in normal fish. Plasma levels of PRL, T4 and cortisol, plasma osmolality, ions (Na+, K+, Ca2+, and Mg2+), glucose, triglyceride, free fatty acids, and amino nitrogen concentrations were similar in the two groups. Cobalt variants thus lack hypophysial pars intermedia and neurohypophysial tissues. Various abnormalities of the cobalt variant, such as the cobalt blue body color and the fat deposition in the abdominal cavity, may be related to the absence of the pars intermedia.
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PMID:Pituitary of "cobalt" variant of the rainbow trout separated from the hypothalamus lacks most pars intermedial and neurohypophysial tissue. 826 55

We have investigated the role of the gonadal steroids testosterone (T) and progesterone in modulating: (1) the onset and severity of adjuvant-induced arthritis (AA), (2) the response of the hypothalamo-pituitary-adrenal (HPA) axis, and (3) the levels of plasma prolactin and anterior pituitary prolactin messenger ribonucleic acid (mRNA) in the rat. Male rats were castrated (CSX) and received either no T, low T or high T delivered using silastic implants. In a second study experimental groups comprised CSX/AA, CSX/AA + progesterone or CSX/AA + progesterone + T. The time of onset was sooner and the severity of AA was greater in CSX rats. Inflammation was prevented by T replacement. Endogenous plasma T levels were decreased in AA rats. In control animals with AA there was an increase in pro-opiomelanocortin (POMC) mRNA in the anterior pituitary and of plasma corticosterone, and a decrease in corticotrophin-releasing factor (CRF) mRNA. These changes in the HPA axis of AA and CSX/AA rats were reversed by T replacement. These data suggest that T has an important protective effect on the progress and severity of AA. This was reflected by a reversal of the neuroendocrine changes of the HPA axis. Progesterone treatment alone had no effect on the severity of the disease. Prolactin mRNA in the anterior pituitary was decreased in the CSX and in the CSX/AA group but was not altered by AA. Plasma prolactin was raised in AA but T replacement did not reduce these elevated levels despite the absence of disease. Thus, prolactin provides a poor indicator of inflammation, suggesting that it may not be a potent pro-inflammatory compound in AA.
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PMID:A protective role for testosterone in adjuvant-induced arthritis. 860 51

Progesterone (P) stimulates prolactin secretion through a neural mechanism in estrogen (E)-primed female monkeys. Several peptides, including beta-endorphin (BE), oxytocin (OT), substance P (SP) and vasoactive intestinal polypeptide (VIP) are potential prolactin stimulatory factors and could mediate the effect of P. We hypothesized that the antagonism of a pivotal peptidergic neural system would block P-induced prolactin secretion and that the function of a pivotal peptidergic system would be altered by changes in gonadal steroid concentrations. Therefore it was of interest (1) to examine the effect of infusion of antagonists to these peptides on P-induced prolactin secretion, and (2) to determine BE, OT, SP and VIP levels in the hypothalamus of monkeys of various reproductive states. For the antagonist studies, female monkeys (n = 8) were spayed, adapted to a vest and tether remote sampling system and catheterized prior to antagonist challenges. E-primed monkeys received P injections 48 h prior to antagonist administration. Prolactin increased within 36-48 h of P injection. All antagonist challenges were administered in varying doses during the P-induced prolactin elevation and blood samples were collected every 10 min for prolactin determinations. The opiate antagonist, naloxone (n = 5), reduced serum prolactin in a dose-related manner with a mean IC50 of 1.5 +/- 0.6 micrograms/kg/min. The OT (n = 4), SP (n = 4) or VIP (n = 4) antagonists did not reduce serum prolactin in a dose-related manner. We previously reported that the hypothalamic content of OT is increased by ovarian hormones. To determine whether the hypothalamic content of BE, SP or VIP was related to gonadal status, the peptide levels in 4 hypothalamic regions of monkeys in various physiological states were measured. BE (ng/mg protein) in the medial basal hypothalamus (MBH) was significantly greater in adult females (17.7 +/- 6.9; n = 6) as compared to spayed females (0.6 +/- 0.2; n = 3) and juvenile females (1.8 +/- 1.1; n = 3). Hypothalamic content of SP in the preoptic area and mammillary bodies, but not the MBH, was significantly greater in gonadal intact females than spayed females. VIP content (pg/mg protein) was not significantly different between adult, spayed and juvenile females nor between adult and juvenile males in any hypothalamic area. Taken together these results support a pivotal role for BE in the neural regulation of P-induced prolactin secretion. The involvement of OT, SP, and VIP in a specific manner at the pituitary level is not indicated.
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PMID:Beta-endorphin, but not oxytocin, substance P or vasoactive-intestinal polypeptide, contributes to progesterone-induced prolactin secretion in monkeys. 879 99

Current evidence indicates that the neuroendocrine system is the highest regulator of immune/inflammatory reactions. Prolactin and growth hormone stimulate the production of leukocytes, including lymphocytes, and maintain immunocompetence. The hypothalamus-pituitary-adrenal axis constitutes the most powerful circuit regulating the immune system. The neuropeptides constituting this axis, namely corticotrophin releasing factor, adrenocorticotrophic hormone, alpha-melanocyte stimulating hormone, and beta-endorphin are powerful immunoregulators, which have a direct regulatory effect on lymphoid cells, regulating immune reactions by the stimulation of immunoregulatory hormones (glucocorticoids) and also by acting on the central nervous system which in turn generates immunoregulatory nerve impulses. Peptidergic nerves are major regulators of the inflammatory response. Substance P and calcitonin gene-related peptide are pro-inflammatory mediators and somatostatin is anti-inflammatory. The neuroendocrine regulation of the inflammatory response is of major significance from the point of view of immune homeostasis. Malfunction of this circuit leads to disease and often is life-threatening. The immune system emits signals towards the neuroendocrine system by cytokine mediators which reach significant blood levels (cytokine-hormones) during systemic immune/inflammatory reactions. Interleukin-1, -6, and TNF-alpha are the major cytokine hormones mediating the acute phase response. These cytokines induce profound neuroendocrine and metabolic changes by interacting with the central nervous system and with many other organs and tissues in the body. Corticotrophin releasing factor functions under these conditions as a major co-ordinator of the response and is responsible for activating the ACTH-adrenal axis for regulating fever and for other CNS effects leading to a sympathetic outflow. Increased ACTH secretion leads to glucocorticoid production. alpha-melanocyte stimulating hormone functions under these conditions as a cytokine antagonist and an anti-pyretic hormone. The sympathetic outflow, in conjunction with increased adrenal activity. leads to the elevation of catecholamines in the bloodstream and in tissues. Current evidence suggests that neuroimmune mechanisms are essential in normal physiology, such as tissue turnover, involution, atrophy, intestinal function, and reproduction. Host defence against infection, trauma and shock relies heavily on the neuroimmunoregulatory network. Moreover, abnormalities of neuroimmunoregulation contribute to the aetiology of autoimmune disease, chronic inflammatory disease, immunodeficiency, allergy, and asthma. Finally, neuroimmune mechanisms play an important role in regeneration and healing.
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PMID:The immune effects of neuropeptides. 891 48

Interleukin-6 (IL-6), the main circulating cytokine, is putatively a major mediator of the effects of the immune system on several endocrine axes and intermediate metabolism. We performed dose-response studies of recombinant human IL-6 on pituitary hormone secretion in 15 healthy male volunteers, using 5 single, escalating subcutaneous doses of IL-6 (0.1, 0.3, 1.0, 3.0 and 10.0 micrograms/kg body weight), each in 3 volunteers. We measured resting metabolic rate (RMR) with indirect calorimetry and plasma anterior pituitary hormones and vasopressin (AVP) at baseline and half-hourly over 4 h after the injection. All doses examined were tolerated well and produced no significant adverse effects. Dose-dependent RMR increases were observed in response to the 3.0- and 10.0-microgram/kg doses of IL-6, beginning at 60 min and slowly peaking between 180 and 240 min. Plasma adrenocorticotropic-hormone concentrations increased dramatically and dose-dependently in all the patients who received the 3.0- and 10.0-microgram/kg doses of IL-6, respectively, peaking to 150 and 255 pg/ml at 60 min, and slowly returning to normal by 4 h. Corresponding plasma cortisol levels peaked dose-dependently between 90 and 150 min, but remained elevated throughout the sampling period. In contrast, the growth hormone (GH) dose-response was bell-shaped, with maximum (approximately 100-fold) stimulation achieved by 3.0 micrograms/kg IL-6. Prolactin (PRL) showed a similar but less pronounced response pattern. Thyroid-stimulating hormone (TSH) dose-dependently and progressively decreased over the 240 min, while gonadotropins showed no clear-cut changes. In conclusion, subcutaneous IL-6 administration induced synchronized dose-dependent increases in the RMR and hypothalamic-pituitary-adrenal axis activity, suggesting that hypothalamic corticotropin-releasing hormone may mediate both of these functions in humans. IL-6 also acutely stimulated GH and PRL secretion and suppressed TSH secretion. The dose of 3.0 micrograms/kg could be used safely in the study of patients with disturbances of the hypothalamic-pituitary unit or of thermogenesis.
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PMID:Dose effects of recombinant human interleukin-6 on pituitary hormone secretion and energy expenditure. 925 19

The anterior pituitary (AP) gland secretes 6 different hormones. Prolactin (PRL) is secreted at a relatively high level without stimulation by the hypothalamus, while secretion of the others requires the action of stimulatory factors from the hypothalamus. In order to gain an insight into the mechanism underlying the different spontaneous release patterns of these hormones, we investigated their spontaneous release rate after pretreating rat anterior pituitary cells with trypsin. Rat AP cells were cultured on Cytodex microcarrier beads for 4 days and were then superfused with either control medium or medium containing trypsin (0.25%) for 5 min. The subsequent release rates of the AP hormones were monitored. The basal release of PRL was severely reduced to almost undetectable level and began to recover 120 min after the trypsin-pretreatment. Full recovery was attained over the next 100 min and was delayed by treatment with a protein synthesis inhibitor, cycloheximide (7 microM). In the trypsin-pretreated cells, basal release of PRL and growth hormone (GH) was severely reduced, while that of thyroid stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH) was enhanced and luteinizing hormone (LH) and follicle stimulating hormone (FSH) was not markedly affected by the treatment, suggesting that the suppression of PRL release was not caused by nonspecific damage to the cells. Since trypsin does not readily enter cells, the altered secretion of AP hormones seems to be the result of restricted digestion of the external components of the cells. On the bases of these observations, we predicted that the mechanism of spontaneous release of hormones involves trypsin sensitive proteins (TSMP) on the plasma membranes of the anterior pituitary cells.
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PMID:Alteration of basal release of anterior pituitary hormones by pretreatment of primary cultured cells with trypsin. 939 66

Data regarding the neuroendocrine response pattern to sexual arousal and orgasm in man are inconsistent. In this study, ten healthy male volunteers were continuously monitored for their cardiovascular and neuroendocrine response to sexual arousal and orgasm. Blood was continuously drawn before, during and after masturbation-induced orgasm and analyzed for plasma concentrations of adrenaline, noradrenaline, cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, growth hormone (GH), beta-endorphin and testosterone. Orgasm induced transient increases in heart rate, blood pressure and noradrenaline plasma levels. Prolactin plasma levels increased during orgasm and remained elevated 30 min after orgasm. In contrast, none of the other endocrine variables were significantly affected by sexual arousal and orgasm.
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PMID:Neuroendocrine and cardiovascular response to sexual arousal and orgasm in men. 969 39

Adults of Rana catesbeiana maintained for 4 days in 12:12 light/dark regimen exhibited a rhythmic color change of 24 hr. Under constant light, however, the rhythm disappeared, and the reflectance values gradually became greater, that is the animals became lighter. Under constant darkness, the rhythm was also abolished, but the animals tended to a darker color. On black background the skin darkening proceeded at a faster rate as compared to the skin lightening of animals adapting to a white background. The difference in color change rate suggests that the darkening responses are probably mediated by an increase in a circulating hormone, whereas skin lightening probably results from the serum level decrease of the same hormone. Most certainly, this hormone is alpha-MSH, as the in vitro assays demonstrated its high potency as a full darkening agonist (EC50 = 9 x 10(-10) M). Prolactin (EC50 = 7.7 x 10(-8) M) and endothelins 2 (EC50 = 1.3 x 10(-6) M) and 3 (EC50 = 4.8 x 10(-7) M) were also full agonists, but 100- to 1000-fold less potent than alpha-MSH. Isoproterenol, in the absence or presence of dibenamine, and endothelin-1 also elicited darkening responses in a dose-related manner, but reaching only 23% and 35% of the maximal darkening, respectively. Isoproterenol darkening effect was completely blocked by propranolol, confirming its action through beta-adrenoceptors. These results, taken together with the lack of lightening activity of norepinephrine on alpha-MSH-darkened skins, suggest that R. catesbeiana melanophores do not possess very active beta-adrenoceptors and lack alpha-adrenoceptors. On the other hand, the lightening agonist melatonin elicited only half-maximal dose-dependent reversal of MSH-induced darkening. Our results suggest that the chromatic rhythm is not endogenous, and most likely is determined by the light/dark cycle effect on alpha-MSH secretion.
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PMID:Physiological color change in the bullfrog, Rana catesbeiana. 991 86


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