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)

Aminoglutethimide is effective in the treatment of breast cancer in postmenopausal patients as a result of its inhibition of aromatase. Its use is complicated by a number of endocrine side-effects which include the inhibition of thyroxine synthesis and inhibition of 11-steroid and 21-steroid hydroxylases. When aminoglutethimide is used at the conventional daily dose of 1000 mg in combination with 40 mg of hydrocortisone these effects can result in clinically significant hypothyroidism and increases in the serum levels of oestrone in response to stimulation of adrenocorticotropic hormone (ACTH). In the current study it was found that with twice daily treatment at the low dose of 125 mg aminoglutethimide plus 20 mg hydrocortisone there was no significant increase in oestrone levels after ACTH stimulation. In addition there was little effect on thyroid function: serum levels of triiodothyronine and thyroxine were unaffected whilst there was a marginally significant (P less than 0.05) increase in thyroid-levels were confined to those patients with pretreatment values greater than 2.5 mU/L, the most marked effect being in 1 patient whose pretreatment level was already outside the normal range.
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PMID:Low-dose aminoglutethimide in postmenopausal breast cancer: effects on adrenal and thyroid hormone secretion. 165 77

Aminoglutethimide at concentrations from 0.1 to 5 nM is able to inhibit the cortisol release elicited by adrenocorticotropic hormone (ACTH) (from 2.5 to 50 ng/ml) in guinea-pig adrenal cortex slices. The antagonism is a non-competitive one (in a Lineweaver-Burk plot), whereas other drugs (morphine, endorphin, indomethacin, etc.) inhibit ACTH competitively. This is in agreement with the known mechanism of action of aminoglutethimide, which inhibits the synthesis of cortisol by blocking reactions of enzymes such as aromatase and desmolase. From the data one can calculate the dissociation constant (Km) of ACTH with its receptor(s) to be 0.27 pg/ml and the inhibiting constant (Kl) of aminoglutethimide to be 49.78 x 10(-10) M. The maximal response of ACTH was 52.9 ng/ml.
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PMID:Antagonism of aminoglutethimide and adrenocorticotropic hormone (ACTH) studied on slices of adrenal glands of the guinea-pig. 255 Feb 4

Aminoglutethimide (Ag) is a potent aromatase-enzyme inhibitor used in the treatment of patients with breast cancer. In the past, it has been administered in doses of 1,000 mg/d (usually with 40 mg hydrocortisone). At these dose levels, the drug also affects multiple cytochrome P-450 enzymes, including enzymes for adrenal steroid biosynthesis. Recently, lower-dose regimens (500 mg/d) of Ag have been found to be just as effective for breast cancer therapy, but less toxic than the higher conventional dose. There is limited information on the adrenal effects at the lower dosages, and it is not known whether these effects are clinically significant. We measured basal and synthetic corticotropin (Cortrosyn)-stimulated levels of adrenal steroids in postmenopausal breast cancer patients before and during treatment with low-dose Ag (500 mg/d) administered without a glucocorticoid preparation. Basal levels of progesterone, 17-OH progesterone, and 11-deoxycortisol were higher after 2 months' treatment (P < .01). After ACTH injection, peak levels of progesterone and 17-OH progesterone were higher (P < .01), but in contrast, peak levels of 18-OH corticosterone were lower during treatment (P < .02). Basal and peak levels of cortisol, aldosterone, and all other adrenal steroids were unchanged during treatment. We conclude that low-dose Ag treatment leads to partial inhibition of the 21-hydroxylase, 11-hydroxylase, and 18-hydroxylase adrenal enzymes. Since cortisol and aldosterone secretion remained normal with minimal shunting to or accumulation of adrenal androgen compounds, we believe that the mild inhibition was compensated for by further endogenous ACTH stimulation.
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PMID:Adrenal effects of low-dose aminoglutethimide when used alone in postmenopausal women with advanced breast cancer. 820 61

The objective of this study was to determine the effects of manipulating glucocorticoid negative feedback on acute ACTH and corticosterone responses to corticotropin-releasing hormone (CRH) injection in 7-day-old rats exposed to normoxia or hypoxia from birth. Chemical adrenalectomy was achieved with aminoglutethimide, and glucocorticoids were replaced with a low dose of dexamethasone. Hypoxia per se increased basal plasma corticosterone and attenuated the plasma ACTH response to CRH. Aminoglutethimide per se decreased plasma corticosterone and strongly increased basal plasma ACTH and anterior pituitary POMC gene expression. Dexamethasone partially attenuated elevations in basal plasma ACTH due to aminoglutethimide in both normoxic and hypoxic pups, but inhibited anterior pituitary POMC expression and CRH-induced plasma ACTH only in hypoxic pups. Despite this inhibition, hypoxic pups treated with both dexamethasone and aminoglutethimide still exhibited a significant CRH-induced increment in plasma ACTH, which was lacking in hypoxic pups not treated with either dexamethasone or aminoglutethimide. We conclude that ACTH responses to acute stimuli in hypoxic neonatal rats are prevented by ACTH-independent increases in corticosterone, rather than by intrinsic hypothalamic-pituitary hypoactivity.
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PMID:Glucocorticoid feedback control of corticotropin in the hypoxic neonatal rat. 1728 45