Effects of enclomiphene and zuclomiphene on basal and gonadotrophin-stimulated progesterone secretion by isolated subpopulations of small and large ovine luteal cells

• Published in: Human reproduction (Oxford) Vol. 11; no. 6; pp. 1250 - 1255
• Main Authors: Opsahl, Michael S., Fitz, Tony A., Rexroad, Caird E., Fritz, Marc A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.06.1996
• Subjects: Animals; Biological and medical sciences; Clomiphene - pharmacology; clomiphene citrate; Corpus Luteum - cytology; Corpus Luteum - drug effects; Corpus Luteum - metabolism; Dose-Response Relationship, Drug; Drug Interactions; Enclomiphene; Estradiol - pharmacology; Female; Fertility Agents, Female; Genital system. Reproduction; in vitro; In Vitro Techniques; lutein cells; Luteinizing Hormone - pharmacology; Medical sciences; ovine; Pharmacology. Drug treatments; Pregnenolone - metabolism; Progesterone - metabolism; Sheep; clomiphene citrate; lutein cells; ovine; Non steroidal estrogen; Estrogen; Clomifene; In vitro; Estradiol; Ovarian hormone; Endocrine secretion; Ovary; Vertebrata; Mammalia; Animal; Female genital system; Corpus luteum; Female; Sheep; Artiodactyla; Progesterone; Sex steroid hormone; Mechanism of action; Ungulata
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/oxfordjournals.humrep.a019367

We examined the effects of enclomiphene and zuclomiphene, alone and in combination with oestradiol, on basal and gonadotrophin-stimulated progesterone secretion by isolated subpopulations of both large (granulosa-lutein) and small (theca-lutein) ovine luteal cells. Isolated large and small luteal cells derived from intact, enucleated ovine corpora lutea were incubated for 48–120 h with or without 22R-hydroxycholesterol or pregnenolone (2.5 μM) and a range of enclomiphene, zuclomiphene, and/or oestradiol concentrations (3–100 μM), both with and without ovine Iuteinizing hormone (100 ng/ml). Spent media were assayed in duplicate for progesterone content by radioimmunoassay. Enclomiphene, zuclomiphene, and oestradiol exhibited equivalent dose-dependent inhibitory effects on basal and gonadotrophin-stimulated small and large ovine luteal cell progesterone secretion under all substrate conditions. Both cell types became more sensitive to clomiphene inhibition with increasing time in culture. In combined treatments, the effects of oestradiol and either enclomiphene or zuclomiphene became additive in longer-term cultures and were never antagonistic In this model system, (i) clomiphene, like oestradiol, appears to inhibit 3β-hydroxysteroid dehy-drogenase activity, (ii) both stereoisomers act as oestrogen agonists, (iii) neither demonstrates any anti-oestrogenic properties, and (iv) both large and small luteal cells become more sensitive to clomiphene inhibition with increasing duration of exposure.