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)

Various drugs and hormones influence the light microscopic and especially the electron microscopic structure of the anterior pituitary and its tumors. Many structural effects are known only from animal experiments since specimens from human pituitaries are mostly not available. The structure of growth hormone (GH) cells is relatively stable. A massive GH cell hyperplasia is known only in rare cases with growth hormone releasing factor (GRF) excess from tumors. Prolactin cells can be stimulated by drugs, neurotransmitters, and hormones which decrease the dopamine inhibition. Adrenocorticotropic hormone (ACTH) cells are stimulated by stress, some hormones, loss of adrenals, and drugs which activate the alpha 1- and beta-receptors or inhibit the alpha 2-receptors. They are suppressed and changed into Crooke's cells by treatment with glucocorticoids. Thyroid-stimulating hormone (TSH) cells increase in number and size in states for overstimulation especially by thyrotropin releasing hormone (TRH). A decrease results from hyperthyroidism and possibly from somatostatin, L-dopa, and dopamine. Gonadotroph cells transform into castration cells in strongly hyperactive states (gonadectomy, antiandrogens, gonadotropin releasing hormone [Gn-RH]agonists, aminoglutethimide). Special types of pituitary adenomas can be treated with drugs which suppress hormone production and proliferation. Dopamine agonists and somatostatin reduce the tumor size of varying proportions of GH secreting adenomas in acromegaly. Ultrastructurally, a decrease of cytoplasmic and nuclear volume and an increase of lysosomes are found. Bromocriptine and other dopamine agonists are established in the treatment of prolactin secreting adenomas. They induce a shrinkage in many cases. Ultrastructurally, a reduction of cellular and nuclear size, an increase in number of secretory granules and of lysosomes, and a reduction of rough endoplasmic reticulum can be demonstrated.
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PMID:Effect of drugs on pituitary ultrastructure. 154 57

Apomorphine (Apo), a D1/D2 Dopamine (DA) agonist, at high doses (500 micrograms/kg) induces a short-lasting insomnia, antagonized by a secondary injection of corticotropin-like intermediate lobe peptide (CLIP, 10 ng); these effects are also observed with hypophysectomized (hypoX) rats. The administration of the serotonin (5-HT) agonist 8-hydroxy-2-di-n-propylamino-tetralin (8-OHDPAT, 0.3 mg/kg) induces also an insomnia which, unlike Apo, is followed by a significant PS rebound. CLIP, again, antagonizes the 8-OHDPAT-induced insomnia. Finally, Bromocriptine (5 mg/kg), an agonist for both DA and 5-HT, induces first an insomnia (antagonized by CLIP), followed by a PS rebound; these effects persist in hypoX rats.
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PMID:Proopiomelanocortin (POMC)-derived peptides and sleep in the rat. Part 2--Aminergic regulatory processes. 196 3

Hypothalamo-pituitary disconnection (HPD) in the sheep results in a two-fold increase in pituitary intermediate lobe (IL) immunoreactive (ir)-alpha-N-acetylated endorphin (NacEP) and ir-alpha-melanocyte-stimulating hormone (alpha MSH) content. The rise in IL NacEP content is accompanied by a markedly altered pattern of processing, in that NacEP1-27 becomes the dominant molecular species with a complementary fall in Nac alpha-EP and Nac gamma-EP. To determine if these effects reflect the loss of descending dopaminergic neuronal input to the IL, we have chronically treated two groups (n = 4 per group) of normal sheep with the dopamine antagonist haloperidol or the dopamine agonist bromocriptine; a group of HPD sheep were also treated with bromocriptine. Acid extracts of IL were diluted and ir-alpha-MSH and ir-NacEP content determined by radioimmunoassay; aliquots were submitted to reversed-phase HPLC and collected fractions similarly assayed. Bromocriptine lowered ir-NacEP and ir-alpha-MSH by about 30%; on HPLC the ir-NacEP profiles, and perhaps to a lesser extent those for ir-alpha-MSH were qualitatively similar to untreated controls. In contrast, haloperidol increased by about 45% both ir-NacEP and ir-alpha-MSH levels and produced a marked change in the ir-NacEP molecular profile, with NacEP1-27 becoming the predominant molecular form and other species representing only minor components in the chromatogram. In the treated HPD group, bromocriptine partially restored the processing profiles previously observed in HPD animals to those found in untreated intact animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dopaminergic agents differentially regulate both processing and content of alpha-N-acetylated endorphin and alpha-MSH in the ovine pituitary intermediate lobe. 256 41

Cultured cells from adult rat anterior pituitaries or intermediate lobes were treated with the proteinase inhibitor tripeptide aldehydes BOC-DPhe-Pro-Arg-H (Boc-fPRH) and DPhe-Pro-Arg-H (fPRH), ovine corticotropin-releasing factor (oCRF), and bromocriptine. One millimolar fPRH stimulated basal, and slightly enhanced oCRF-induced ACTH release by melanotrophs in short-term experiments. The basal release of alpha-MSH was also stimulated by the drug. In long-term experiments, fPRH elevated markedly both the release and the intracellular level of ACTH; BOC-fPRH caused an increased alpha-MSH release. Tritiated fPRH had no preference for POMC-producing cells and BOC-fPRH or fPRH were harmless to the cell morphology. In anterior pituitary cell cultures, fPRH diminished slightly basal and oCRF-induced ACTH release. Bromocriptine was ineffective on corticotrophs, however, in melanotrophs it inhibited ACTH release markedly with or without fPRH in the medium. The dissimilar responsiveness of the corticotrophs and melanotrophs to the peptide aldehydes may be interpreted in terms of their differing membrane receptors or intracellular mechanism of stimulus-secretion coupling.
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PMID:Dissimilar responsiveness of cultured corticotrophs and melanotrophs to tripeptide aldehydes. 301 10

Bromocriptine, a dopamine agonist that blocks the secretion of MSH, inhibits melanogenesis in the hair follicular melanocytes of pubertal C3H-HeAvy mice. However, since this effect cannot be explained by a reduction in circulating alpha-MSH, we have examined the possibility that dopaminergic mechanisms may have a direct inhibitory effect on these melanocytes. Bromocriptine decreased tyrosinase activity in skin explants from 30- to 35-day-old mice that were growing dark hair. This decrease in tyrosinase activity was blocked by dopamine receptor antagonists, haloperidol or spiperone. The specific D2 agonist LY 171555 also inhibited tyrosinase activity in the skin explants in a dose-related manner and the effect was blocked by sulpiride, a D2-receptor antagonist. Neither bromocriptine nor LY 171555 had any effect on tyrosinase activity in skin explants taken from adult mice that were growing yellow hair. The D1-receptor agonist SKF 38393 had no effect on tyrosinase activity in skin explants from either group of mice. The present results support the idea that dopamine D2-receptor agonists have a direct inhibitory effect upon tyrosinase activity of hair follicular melanocytes of the C3H-HeAvy mouse. However, this effect was confined to periods of dark hair growth when the melanocytes produce eumelanin. The D2 agonists were ineffective in reducing tyrosinase activity during adult life when the melanocytes produce predominantly phaeomelanin. This suggests that different control mechanisms may operate in the hair follicular melanocytes during periods of eumelanin and phaeomelanin synthesis.
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PMID:Dopaminergic inhibition of tyrosinase activity in hair follicular melanocytes of the mouse. 309 85

Bromocriptine treatment in rats (3 mg/kg per day, 7 days) significantly reduced alpha-msh and aldosterone plasma levels 2 hrs after the final treatment in animals on low, normal and high sodium diets. Alpha-MSH dose response curves for corticosterone and 18-hydroxydeoxycorticosterone (18-OH-DOC) in subsequently incubated glomerulosa cells gave stimulation at lower concentrations of alpha-MSH (10(-10) moles per litre) than in cells from untreated animals (10(-9) moles per 1). Curves for aldosterone (ald) and 18-hydroxycorticosterone (18-OH-B) were also affected in cells from animals on a low sodium diet. Fasciculata-reticularis cell responses to ACTH were unaffected. Metoclopramide (4 mg/kg per day, 7 days) elevated plasma alpha-MSH, although ald was unaffected, but inhibited the glomerulosa cell response to alpha-MSH in vitro. Acute dopaminergic responses in plasma ald may be mediated through alpha-MSH in rats, but chronically alpha-MSH may down- regulate glomerulosa cell alpha-MSH receptors. It is unlikely that alpha-MSH mediates the adrenocortical response to sodium depletion.
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PMID:Dopaminergic control of aldosterone: modulation of the response of rat adrenal zona glomerulosa cells to alpha-Msh by pretreatment with bromocriptine or metoclopramide. 628 Mar 45

A dopaminergic mechanism has been proposed to suppress aldosterone secretion. To assess the possibility that a defect in the dopaminergic mechanism might enhance aldosterone secretion in hypertensive patients, we determined basal and adrenocorticotropic hormone (ACTH)-stimulated plasma aldosterone (PA), cortisol, renin activity, and potassium concentrations before and during dopamine receptor stimulation with dopamine infusion and bromocriptine administration and dopamine receptor blockade with metoclopramide. The patient study groups included: (a) seven patients with low-renin hypertension and abnormal aldosterone suppression with sodium loading and presumed bilateral zona glomerulosa hyperplasia (ZGHP); (b) two patients with aldosterone-producing adenoma; (c) five patients with low-renin hypertension but normal aldosterone suppression with sodium loading; and (d) six patients with normal-renin hypertension. Dopamine infusion in patients with ZGHP caused PA to fall (P less than 0.01) into the normal range, but did not block the enhanced (P less than 0.05) aldosterone response to ACTH that is characteristic of these patients. Dopamine infusion in patients with low-renin hypertension but normal aldosterone suppression also suppressed PA (P less than 0.01), whereas it had no effect upon PA in patients with normal-renin hypertension or aldosterone-producing adenoma and did not blunt the PA response to ACTH in either group. Bromocriptine administration had no effect upon basal or ACTH-stimulated PA. Dopamine infusion in patients with ZGHP also enhanced (P less than 0.05) diuresis and natriuresis in comparison with normal-renin patients. Metoclopramide administration increased (P less than 0.01) PA in all patients. Thus, a dopaminergic mechanism appears to be important in the regulation of aldosterone secretion in patients with ZGHP and in other low-renin hypertensives with normal aldosterone suppression with sodium loading. In contrast, this latter group does not exhibit an enhanced aldosterone response to ACTH. Both of these groups differ from normal-renin hypertensives, who have no PA suppression with dopamine infusion.
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PMID:Aldosterone suppression with dopamine infusion in low-renin hypertension. 630 9

The responses of rat adrenal zona glomerulosa cells to stimulation by alpha-MSH and ACTH and related peptides have been studied. The major findings were that: (1) alpha-MSH stimulated corticosterone production in glomerulosa cells from from normal animals at concentrations of about 10(-10) mol/l, but other steroids, including aldosterone, were not significantly stimulated until levels of 10(-7) mol/l were used. Peptide structure-function relationships showed that in the adrenal cortex, in contrast with other systems, ACTH 4-10 had no effect and did not block the response of glomerulosa cells to alpha-MSH, bisacetyl Ser 1-alpha-MSH, (nor-valine-12)-alpha-MSH, and ACTH 1-13 amide were equipotent with alpha-MSH, while alpha-MSH 1-10 had activity but was considerably less potent. alpha-MSH 6-13, 7-13, 8-13 and lys-11-acetyl-alpha-MSH were all inactive. N-formyl-N-epsilon-benzyloxycarbonyl alpha-MSH stimulated only at 10(-6) mol/l. (2) Normalised alpha-MSH dose-response curves for aldosterone production in glomerulosa cells from normal rats, and corticosterone in inner zone cells were coincident. In glomerulosa cells, prior sodium depletion shifts the dose-response curve for aldosterone to the left, indicating a more sensitive response, and for corticosterone to the right. Bromocriptine treatment (which depresses the level of alpha-MSH in circulating plasma) and metoclopramide (which enhances it) respectively increased and decreased the sensitivity of the response of corticosterone to alpha-MSH in subsequently incubated glomerulosa cells, but had no effect on aldosterone. (3) In contrast, normalised ACTH stimulated dose-response curves for glomerulosa corticosterone and aldosterone, and for fasciculata corticosterone production were all coincident, and were unaffected by sodium depletion, or by metoclopramide or bromocriptine pretreatment. (4) Cyclic-AMP production by glomerulosa cells was stimulated by alpha-MSH only at levels of in excess of 10(-5) mol/l, five orders of magnitude greater than required to produce significant corticosterone stimulation. Under cyclic-AMP stimulation, the normalised responses of glomerulosa corticosterone and aldosterone, and of inner zone corticosterone were all coincident. The data suggest that alpha-MSH at low concentrations (less than 10(-7) mol/l) interacts with a glomerulosa cell receptor which is distinct from the ACTH receptor but interacts with the ACTH receptor at concentrations greater than 10(-'5) mol/l. Corticosterone production is stimulated by alpha-MSH in cells from normal animals at concentrations within the normal range for circulating plasma (approximately 3 X 10(-10) mol/l), while aldosterone is stimulated by similar concentrations of alpha-MSH in cells from sodium depleted animals. The effects of sodium depletion are not modulated through changes in plasma alpha-MSH levels. At low concentrations alpha-MSH stimulation of glomerulosa cells is unlikely to be modulated by cyclic-AMP as second messenger.
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PMID:alpha-MSH and zona glomerulosa function in the rat. 631 Feb 42

Advances in CT scanning and digital subtraction angiography have improved the accuracy of preoperative diagnosis of pituitary disease. Modern radioimmunoassay techniques are able to evaluate "subdivisions" and "relatives" of the classic pituitary hormones, including monomeric and oligomeric growth hormones, somatomedin C, beta-lipotropin, and beta-endorphin, as well as the alpha subunit of follicle-stimulating hormone. Pituitary pathologic states can now be identified immunologically in patients in whom results of radiologic studies are normal. Bromocriptine, a centrally active dopamine antagonist and ergot derivative, is effective in the treatment of prolactinomas, but it is not effective in the treatment of acromegaly. Transsphenoidal surgery remains the treatment of choice in adults with pituitary-dependent Cushing's disease. The surgical advantages of the sublabial, transseptal, transsphenoidal approach include wide-field pituitary accessibility via a midline exposure.
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PMID:Pituitary surgery: current status, including transsphenoidal surgery. 638 85

A case report is presented of the need for both bromocriptine and human menopausal gonadotropin (hMG) for induction of ovulation in a patient who developed partial hypopituitarism and persistent hyperprolactinemia even after a transsphenoidal pituitary microadenectomy. The patient, a 27-year old white female, initially presented in 1979 with a history of amenorrhea and galactorrhea after discontinuing oral contraceptives (OCs). Her menstrual cycles had been regular since her menarch at age 13 until she began taking OCs at age 20. Preoperative endocrine evaluation in 1979 revealed serum luteinizing hormone (LH), 9.1 mIU/ml; serum follicle stimulating hormore (FSH), 6.4 mIU/ml; serum thyroid stimulating hormone (TSH), 3.8 mIU/ml; serum prolactine (PRL), 300 ng/ml; serum thyroxine (T4), 6.4 mcg/dl; and an attenuated PRL response to thyrotropin releasing hormone (TRH). Radiographic studies revealed a pituitary tumor of approximately 1 cm in diameter. In July 1979 a transsphenoidal hypophysectomy was performed. Pathologic examination revealed a pituitary adenoma with a monomorphic basophilic cell population with fibrosis and chronic inflammation. The patient required prednisone therapy postoperatively for 3 months secondary to compromised adrenal status. Prednisone therapy was discontinued in October 1979 after a normal cortisol (F) response to induced hypoglycemia was documented. The patient's serum PRL levels remained elevated at 111 ng/ml in August 1979 and 269 ng/ml in October 1979. Her amenorrhea and galactorrhea persisted. Bromocriptine therapy, 2.5 mg 3 times daily, was instituted in October 1979. She became normoprolactinemic, with a serum PRL of 6 ng/ml, and the galactorrhea disappeared but the amenorrhea persisted. In February 1981 she was referred for further consultation on her fertility status. Bromocriptine therapy was discontinued. In April 1981 she underwent a thorough endocrine evaluation. The results indicate that GnRH stimulation was unable to elicit a pituitary gonadotropin response anywhere near normal levels of FSH and LH, thus suggesting pituitary hypogonadotropism. Growth hormone release was subnormal in response to the insulin induced hypoglycemia and L-dopa ingestion. Hyperprolactinemia was obvious but the patient's serum TSH, T4, and adrenocorticotropin (ACTH) levels were normal. A diagnosis of hyperprolactinemia with partial hypopituitarism and gonadotropin deficiency was made. Bromocriptine therapy was reinstituted at 2.5 mg twice daily in June 1981, with good results. In November 1981 her serum PRL was normal, and as she was desirous of pregnancy, ovulation induction with bromocriptine and Pergonal was carried out. The patient is now 6 months pregnant and doing well. This case illustrates the poor functional results for surgery for pituitary microplactinomas.
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PMID:Partial hypopituitarism and hyperprolactinemia: successful induction of ovulation with bromocriptine and human menopausal gonadotropins. 681 37


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