Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DOC and DOC-SO4, which are present in large amounts in the blood of pregnant women, are derived from sources other than maternal adrenal. Other investigators demonstrated that treatment of near-term pregnant women with ACTH or dexamethasone did not cause alterations in the blood levels of DOC. To define the source(s) of DOC and DOC-SO4 in plasma of pregnant women, we evaluated the conversion of plasma progesterone (P) to DOC in extraadrenal sites. DOC is formed from plasma P and, provided that the pregnancy is one characterized by the usual large production of estrogen, DOC production in a given woman is proportional to the level of P in plasma. Unlike other steroid conversions or interconversions, however, the fractional conversion of P to DOC among apparently normal persons varied widely 0.011 +/- 0.003 (mean +/- SEM, n = 40, range = 0.001 to 0.030). In women pregnant with a normal living fetus, the product of the production rate of P and the fractional conversion of P to DOC is sufficient to account for the majority of DOC produced in the mother. There may be a second source of DOC, i.e. the transfer of DOC from the fetal to the maternal compartment in a manner that involves (a) direct transfer of DOC by way of trophoblast and (b) by desulfurylation of DOC-SO4 from fetal umbilical arterial plasma in trophoblast and thence transfer of DOC liberated in trophoblast to the maternal compartment. Presently, it is clear that DOC-SO4 in blood of pregnant women is not derived from plasma DOC; and there is little or no evidence in support of the proposition that DOC-SO4 (as a sulfoconjugate) is transferred from the fetal to the maternal compartment because of placental hydrolysis to DOC. Among the extraadrenal tissue sites identified as those in which 21-hydroxylation of plasma P could be effected are some also believed to be tissue sites of mineralocorticosteroid action, viz, kidney, aorta, thymus, and spleen. Quantitatively, the origin of DOC in the fetus is not as clear as in the maternal compartment; yet, many tissues of the fetus have been identified in which both steroid 21-hydroxylase and 21-hydroxysteroid sulfotransferase activity are present. Thus, in the human fetus, extraadrenal as well as adrenal production of DOC and DOC-SO4 are possible.
 ...
PMID:The origin of and metabolic fate of deoxycorticosterone and deoxycorticosterone sulfate in pregnant women and their fetuses. 632 63

We have reported previously that during the third trimester of pregnancy a significant portion of DOC in the maternal compartment arises by extraadrenal, 21-hydroxylation of maternal plasma progesterone. Moreover, the increase in DOC observed in plasma of women during the luteal phase of the ovarian cycle, when plasma concentrations of progesterone are elevated, can be attributed to increased DOC formation in extraadrenal sites. In the present study, we sought to ascertain if progesterone is converted to DOC in adult, nonpregnant, female rhesus monkeys to establish this species as an animal model for further investigation of extraadrenal mineralocorticosteroid biosynthesis. We measured the transfer constant of conversion of progesterone to DOC in plasma [( rho]P-DOCBB) from the 3H: 14C ratio of DOC in plasma after a 4 h infusion of [3H]progesterone and [14C] DOC into anesthetized monkeys. The [rho]P-DOCBB was 0.014 +/- 0.004 (mean +/- SEM, N = 7) in the animals studied. The values obtained for [rho]P-DOCBB ranged from 0.006 to 0.04 among the animals studied, a range of values similar to that observed in pregnant and nonpregnant women, men, and adrenalectomized persons. On the basis of these data, we conclude that the rhesus monkey may be an appropriate animal model for further study of extraadrenal steroid 21-hydroxylase activity.
 ...
PMID:Conversion of plasma progesterone to deoxycorticosterone in nonpregnant Macaca mulatta: an animal model for the study of extraadrenal steroid 21-hydroxylase activity. 636 94

The 21-hydroxylation of plasma progesterone (P) has been demonstrated in pregnant, nonpregnant, and adrenalectomized women and in men. The fractional conversion of plasma progesterone to deoxycorticosterone (DOC), [rho]P-DOC BU, among those subjects was 0.009 +/- 0.001 (mean +/- SEM, n = 32). The [rho]P-DOC BU in a woman with congenital adrenal hyperplasia due to apparent adrenal steroid 21-hydroxylase deficiency was 0.010 when she was taking cortisone acetate, and the [rho]P-DOC BU determined when she was not taking cortisone acetate was 0.012. Moreover, the value computed for the fractional conversion of 17 alpha-hydroxyprogesterone to 11-deoxycortisol in this woman (0.004) was similar to that observed in a woman with normal adrenal function (0.005). Therefore, extraadrenal 21-hydroxylase activity in a woman with nonsalt-losing congenital adrenal hyperplasia due to 21-hydroxylase deficiency was similar to that found in persons with normal adrenal function.
 ...
PMID:Extraadrenal steroid 21-hydroxylase activity in a woman with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. 660 Jan 68