Ovine placental steroid 17α-hydroxylase/C-17,20-lyase, aromatase and sulphatase in dexamethasone-induced and natural parturition

J. I. Mason, J. T. France, R. R. Magness, B. A. Murry, C. R. Rosenfeld

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Abstract

Parturition in the sheep is preceded by an abrupt alteration in placental steroid metabolism causing a shift from progesterone to oestrogen production. This change is believed to be a consequence of the prepartum rise in cortisol in the fetal circulation and involves increases in activities of the enzymes steroid 17α-hydroxylase (cytochrome P-450(17α)), steroid C-17,20-lyase, and possibly aromatase and steroid sulphatase. The activity levels have been determined of steroid 17α-hydroxylase, aromatase and steroid sulphatase in placental microsomes in late pregnancy, dexamethasone-induced labour and in natural labour at term. Over the gestational period of 118-140 days, basal levels of placental aromatase were relatively constant (mean value (±S.E.M.) of 5.6 ± 0.5 pmol/min per mg microsomal protein (n = 10)). Pregnenolone and progesterone 17α-hydroxylase activities were undetectable (<0.5 pmol/min per mg microsomal protein (n = 7)). In six animals in labour induced with infusion of dexamethasone into the fetus, placental aromatase activity increased to a value of 14.0 ± 1.0 pmol/min per mg protein; placental pregnenolone 17α-hydroxylase, measured in four of the animals, also increased to 453 ± 77 pmol/min per mg microsomal protein. In five animals in natural spontaneous labour with vaginal delivery, aromatase activity was 26.7 ± 5.2 pmol/min per mg microsomal protein and pregnenolone 17α-hydroxylase activity was 141 ± 14 pmol/min per mg microsomal protein. Steroid sulphatase activity was barely detectable (<1.5 pmol/min per mg microsomal protein) during late pregnancy, dexamethasone-induced labour or natural parturition. Immunoblotting of placental microsomal preparations with a specific antibody to cytochrome P-450(17α) indicated that the glucocorticoid-induced activity of steroid 17α-hydroxylase was associated with an increased content of cytochrome P-450(17α). The cotyledon can then convert pregnenolone to dehydroepiandrosterone and thereby generate aromatizable C19 steroids for the aromatase system to facilitate oestrogen synthesis. Importantly, the ovine placental steroid 17α-hydroxylase inefficiently metabolizes 17α-hydroxyprogesterone to androstenedione and thus progesterone is not a principal precursor of oestrogen. The data are consistent with a mechanism of glucocorticoid action in natural ovine parturition to increase cytochrome P-450(17α) synthesis either by stabilizing the mRNA for cytochrome P-450(17α) or else acting as a stimulus to transcription of the steroid 17α-hydroxylase gene.

Original languageEnglish (US)
Pages (from-to)351-359
Number of pages9
JournalJournal of Endocrinology
Volume122
Issue number1
StatePublished - 1989

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Steroid 17-alpha-Hydroxylase
Sulfatases
Aromatase
Dexamethasone
Sheep
Pregnenolone
Parturition
Cytochrome P-450 Enzyme System
Steryl-Sulfatase
Induced Labor
Mixed Function Oxygenases
Proteins
Progesterone
Estrogens
Steroids
Glucocorticoids
17-alpha-Hydroxyprogesterone
Pregnancy
Dehydroepiandrosterone
Cotyledon

ASJC Scopus subject areas

  • Endocrinology

Cite this

Ovine placental steroid 17α-hydroxylase/C-17,20-lyase, aromatase and sulphatase in dexamethasone-induced and natural parturition. / Mason, J. I.; France, J. T.; Magness, R. R.; Murry, B. A.; Rosenfeld, C. R.

In: Journal of Endocrinology, Vol. 122, No. 1, 1989, p. 351-359.

Research output: Contribution to journalArticle

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