ANDROGEN BIOSYNTHESIS IN THE STOMACH - EXPRESSION OF CYTOCHROME-P450 17-ALPHA-HYDROXYLASE 17,20-LYASE MESSENGER-RIBONUCLEIC-ACID AND PROTEIN, AND METABOLISM OF PREGNENOLONE AND PROGESTERONE BY PARIETAL-CELLS OF THE RAT GASTRIC-MUCOSA/

Dehydroepiandrosterone (DHEA) and its conjugates persist in the rat br ain, for up to 1 month after ablation of both adrenals and gonads. Sin ce DHEA synthesis in brain from pregnenolone (PREG) was excluded, we h ave considered other tissular sources including the digestive tract. I n. situ hybridization with specific oligonucleotide probes showed that the parietal cells of the gastric mucosa, contrary to other cell type s, strongly expressed P450(17 alpha) messenger RNA. Expression of the enzyme in the parietal cells was confirmed by immunocytochemistry with specific antibodies. An intense reaction was observed in the stomach of adult males and of cyclic or pregnant females. Access to food did n ot influence the intensity of immunostaining. It appeared at postnatal days 16-21, then the number of positive cells increased rapidly and l eveled off at adult age. Parietal cells were released by pronase diges tion of everted stomachs from adult male and female rats and were puri fied by density gradient centrifugation on Nycodenz. 5 x 10(4) to 1.6 X 10(6) cells were incubated with either 1 mu M C-14-PREG or C-14-prog esterone (C-14-PROG) at 37 C under 95% O-2-5% CO2, for 10-180 min. PRE G was converted to 17-OH PREG and to androstenediol, whereas PROC was converted to 17-OH PROC and to testosterone. Only minute amounts of ei ther DHEA or androstenedione, respectively, were detected at any incub ation time, indicating their fast conversion to the corresponding 17 b eta-hydroxysteroids. H-3-25-OH cholesterol was not metabolized to H-3- PREG, and C-14-PREG was not converted to C-14-PROG, in accordance with negative immunocytochemical results with antibodies to cytochrome P45 0(scc) and SP-hydroxysteroid dehydrogenase Delta 5 --> 4-isomerase (3 beta-HSD). In conclusion, the parietal cells, which are known as the s ource of gastric acid secretion, can synthesize testosterone from FROG and androstenediol from PREG. The physiological relevance of such con versions remains to be established.