Immunoreactive cytochrome P-45017  in rat and guineapig gonads, adrenal glands and brain

Abstract

The cytochrome P-450(17 alpha)-hydroxylase, 17----20 lyase (P-450(17 alpha)) is the key enzyme responsible for the biosynthesis of androgens in steroidogenic organs. Its cellular localization has been examined with an immunohistochemical technique. In immature rat ovary, P-450(17 alpha) was first detected in sparse interstitial cells on postnatal Day 8. The number of immunoreactive interstitial cells increased thereafter and the intensity of P-450(17 alpha) staining in these cells was highest at 3 weeks of age. The intensity of staining then started to decline and was very faint at Day 35. From 6 weeks on, the distribution of immunoreactive P-450(17 alpha) was of the adult type: it was detected exclusively in the thecal cells of the large antral, preovulatory, follicles. P-450(17 alpha) was not detectable during pregnancy except on the day of parturition, when thecal cells were transiently immunoreactive. The staining had vanished 24 h after delivery. Human chorionic gonadotrophin (hCG), injected into immature females on Days 24 to 26, induced P-450(17 alpha) prematurely in thecal cells. When injected on Days 12 to 14 of pregnancy, hCG also induced P-450(17 alpha) in the thecal cells surrounding the largest follicles, whereas the interstitial and luteal cells were not immunostained. The antiprogestin RU486, injected on Day 16 of pregnancy, reinstated P-450(17 alpha) (and P-450scc) immunoreactivity in the thecal cells. Oestradiol selectively suppressed P-450(17 alpha) expression in the thecal cells of RU486-treated females. In immature guinea-pig ovary, P-450(17 alpha) was immunostained in thecal cells, not in interstitial cells, although the interstitial cells expressed the delta 5-3 beta-hydroxysteroid dehydrogenase. P-450(17 alpha) was also immunolocalized in the Leydig cells of rat and guinea-pig testes, and in the guinea-pig adrenal cortex (zonae fasciculata and reticularis), but not in the rat adrenal cortex. P-450(17 alpha) was not detectable in the brain of either rat or guinea-pig.

Immunolocalization and Biochemical Determination of Cytochrome P450C17 in Adrenals of Hamsters Treated with ACTH

“…Le Goascogne et al (1991) reported immunoreactive P450C17 in rat gonads but not in the adrenals, thus confirming the absence of expression of this cytochrome in this species. In the mouse, Keeney et al (1995) reported clusters of fetal adrenal cells that hybridize specifically with murine P450C17 cRNA.…”

“…1996). The results obtained in the guinea pig and the pig demonstrated that P450C17 was present only in the zonae fasciculatae (ZF) and reticularis, with intense immunoreactivity in cells of the outer fasciculata zone and decreasing intensity towards the reticularis cells (Shinzawa et al 1988;Le Goascogne et al 1991;Colby et al 1993). In the adrenal cortex of the rat, however, no immunoreactivity could be detected, which is in accordance with the fact that their adrenal glands do not express P450C17 (Van Weerden et al 1992).…”

“…Immunohistochemical methods have proved to be highly useful for investigation of the zonal distribution of the adrenal enzymes. The zonal distribution of P450C17 has been studied in the adrenal cortex of the guinea pig (Shinzawa et al 1988;Le Goascogne et al 1991;Colby et al 1993), rat (Le Goascogne et al 1991), pig (Sasano et al 1989), Rhesus monkey (Mesiano et al 1993), and the human fetus (Mesiano et al 1993;Breault et al . 1996).…”

Antenatal Treatment with Glucocorticoids and the Hypotalamic-Pituitary-Adrenal Axis

“…Klju~ne re~i: programiranje, fetalni razvoj, HPA osovina, deksametazon, betametazon, antenatalna terapija pus luteum and in the fetal gonads (10). Thus, the placenta and the fetal adrenals make a unique fetoplacental functional unit that controls and adjusts HPA axis functioning during in utero development.…”

Central Administration of a Cytochrome P450-7B Product 7α-Hydroxypregnenolone Improves Spatial Memory Retention in Cognitively Impaired Aged Rats

“…Blood levels of dehydroepiandrosterone (DHEA) in humans decline significantly with age and parallels cognitive decline (Orentreich et al, 1992). Rodents, in contrast, have very little DHEA in brain because of the lack (or undetectable levels) of cyp17␣ (17␣-hydroxylase) that catalyzes the conversion of pregnenolone (PREG) to DHEA in rat and mouse adrenal cortex (Le Goascogne et al, 1991;Mellon and Deschepper, 1993). However, high levels of PREG, the neurosteroid precursor of DHEA, can be detected in the hippocampus of young rats, whereas aged rats have lower levels, which correlate with cognitive deficits .…”