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Search for other papers by J. S. JENKINS in
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SUMMARY
The metabolism of testosterone by skin from patients with disorders of hair growth in the presence of normal testosterone levels has been studied in vitro and compared with the metabolic activity of normal skin. The main metabolites formed were dihydrotestosterone, androstenedione, androsterone and androstanedione. In four out of six females with hirsutism, the skin produced increased amounts of dihydrotestosterone and also androstenedione. A patient with the rare condition of unilateral hirsutism showed no difference in metabolic activity between the hirsute and non-hirsute sides. In localized failure of androgenically determined hair growth, seen in three beardless males, the metabolism of the hairless area was greater than that of the normally hairy abdomen. Four patients with testicular feminization and complete absence of body hair were studied and the formation of dihydrotestosterone ranged from low to high normal levels.
Search for other papers by J. S. JENKINS in
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Search for other papers by S. ASH in
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SUMMARY
The metabolism in vitro of testosterone by normal human skin has been studied and the results have been compared with those obtained in two cases of testicular feminization. The predominant metabolite was 5α-dihydrotestosterone followed by androstenedione, androsterone, and 5α-androstanedione.
Suprapubic skin from patients with testicular feminization metabolized testosterone in a completely normal manner. There was no evidence to support the view that a failure to produce an essential metabolite of testosterone is responsible for the condition of testicular feminization.
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Abstract
Although corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) have been extensively characterized as stimulators, and glucocorticoids as inhibitors of ACTH secretion, far less is known about the control of the secretion of ACTH precursors from the anterior pituitary or about the types of corticotrophs involved. The present study was designed to systematically evaluate the actions of stimulatory and inhibitory factors on the secretion of ACTH and ACTH precursors (pro-opiomelanocortin, M r 31 000; pro-ACTH, M r 22 000) from dissociated ovine anterior pituitary cells. The cells were stimulated for 3 h with CRH (10 nmol/l) and AVP (100 nmol/l), alone or in combination with the synthetic glucocorticoid dexamethasone. In designated wells, cells were treated with dexamethasone, (100 nmol/l), beginning 16–18 h before and continuing through the 3-h secretion experiments in the presence of CRH and AVP. Secretion of ACTH-like peptides from intact cultures was compared with that from cultures which had been pretreated with a cytotoxic CRH conjugate (cytotoxin) to eliminate CRH-target cells specifically. Immunoreactive (ir)-ACTH was measured by radioimmunoassay (RIA); ACTH(1–39) and ACTH precursors were specifically measured by two-site immunoradiometric assays that discriminate between the two. In intact populations of cells, dexamethasone had no effect on basal ACTH(1–39) secretion, but decreased the secretion of ACTH(1–39) in response to CRH or AVP. Pretreatment of cells in the same experiments with cytotoxin (for 18 h, beginning 3·5 days before secretion studies) also had no significant effect on basal ACTH(1–39) secretion, but eliminated the response to CRH and decreased the response to AVP. In contrast to the situation in intact populations, dexamethasone had no effect on the residual secretion of ACTH(1–39) in response to AVP. These results mirrored those for secretion of ir-ACTH, measured by RIA.
Secretion of ACTH precursors followed a different pattern from that for ir-ACTH and ACTH(1–39). In intact populations, dexamethasone decreased the secretion of ACTH precursors in response to CRH, but had no effect on basal secretion or the precursor response to AVP. Elimination of CRH-target cells also had no effect on basal precursor secretion and eliminated the secretion of precursors in response to CRH. Loss of CRH-target cells was accompanied by a smaller decrease in the secretion of ACTH precursors than ir-ACTH and ACTH(1–39) in response to AVP. Interestingly, dexamethasone significantly increased the secretion of ACTH precursors in response to AVP after cytotoxin.
These results suggest either that the inhibition by glucocorticoids of the ACTH(1–39) secretory response to AVP is confined to those AVP-responsive cells that are sensitive to the CRH-target-specific cytotoxin, or that glucocorticoid-induced inhibition of the response to AVP depends on the functional presence of CRH-responsive cells. The results further suggest that the secretion of ACTH precursors in response to AVP is resistant to inhibition by glucocorticoids, regardless of the presence of CRH-target cells and is, generally, much less influenced by, or dependent upon, CRH-target cells. Taken together, the data suggest that those corticotrophs which are resistant to cytotoxin are the source of ACTH precursors secreted in response to AVP, and resist inhibition by glucocorticoids.
Journal of Endocrinology (1994) 140, 189–195