Reference

Clomiphene and tamoxifen inhibit progesterone synthesis in granulosa cells: comparison with estradiol

Clomiphene and tamoxifen inhibit progesterone synthesis in granulosa cells: comparison with estradiol. Sgarlata, C. S.; Mikhail, G.; Hertelendy, F. (Sch. Med., St. Louis Univ., St. Louis, MO 63104, USA). Endocrinology (Baltimore), 114(6), 2032-8 (English) 1984. CODEN: ENDOAO. ISSN: 0013-7227. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) The actions of clomiphene [911-45-5], tamoxifen [10540-29-1], and 17b-estradiol [50-28-2] were studied in an isolated avian granulosa cell system during short term incubations. A dose-dependent inhibition of ovine LH [9002-67-9]-enhanced progesterone [57-83-0] prodn. was obsd. for all 3 compds., with an IC50 of 3 ′ 10-6 M and maximal inhibition (95%) at 5 ′ 10-5 M. A similar inhibition was found when cells were stimulated by either 8-bromo-cAMP [23583-48-4] or forskolin [66575-29-9]. Neither clomiphene nor tamoxifen had an inhibitory effect on the conversion of pregnenolone [145-13-1] to progesterone, a step that was blocked by 17b-estradiol and isoxazole, a known inhibitor of 3b-hydroxysteroid dehydrogenase [9015-81-0]. However, cells exposed to clomiphene failed to use 6-3H-labeled 25-hydroxycholesterol [2140-46-7], but estradiol increased the conversion of labeled substrate to pregnenolone at the expense of progesterone. These triphenylethylene compds., which are used clin. as antiestrogens, inhibit steroidogenesis at a step before pregnenolone formation, probably at the site of the cholesterol side-chain cleavage enzyme complex, whereas 17b-estradiol inhibits 3b-hydroxysteroid dehydrogenase.

Hydrocortisone elicits the effect of clomiphene citrate on luteinizing hormone-releasing hormone release in vitro

Hydrocortisone elicits the effect of clomiphene citrate on luteinizing hormone-releasing hormone release in vitro. Miyake, Akira; Tasaka, Keiichi; Sakumoto, Tetsuro; Nagahara, Yasuhito; Aono, Toshihiro (Med. Sch., Osaka Univ., Osaka 553, Japan). Acta Endocrinol. (Copenhagen), 107(2), 145-8 (English) 1984. CODEN: ACENA7. ISSN: 0001-5598. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) The effect of hydrocortisone [50-23-7] on the release of LH [9002-67-9] and LH-RH [9034-40-6] in response to clomiphene [911-45-5] was examd. in a sequential double chamber perifusion system by perifusing mediobasal hypothalami (MBH) and(or) pituitaries excised from normal female rats in diestrus. When the MBH and the pituitary were perifused in sequence with medium contg. hydrocortisone (5 ′ 10-6M), a 100-150% increase in LH release was obsd. 40 min after the administration of clomiphene (3 ′ 10-8 mol). Clomiphene had no effect on LH release from the pituitary when perifused in series with the MBH without basal hydrocortisone infusion. Administration of clomiphene did not increase LH release from the pituitary perifused alone, with, or without medium contg. hydrocortisone. The concn. of LH-RH in the efflux was increased 40 min after clomiphene administration when MBH was perifused with medium contg. hydrocortisone, whereas clomiphene had no effect when perifused with medium only. Apparently, hydrocortisone stimulates the effect of clomiphene on LH-RH release from the hypothalamus, which in turn induces LH release from the pituitary.