Synergistic effect of glucocorticoids and androgens on the hormonal induction of tissue plasminogen activator activity and messenger ribonucleic acid levels in granulosa cells

• Published in: Molecular and cellular endocrinology Vol. 68; no. 2; pp. 143 - 151
• Main Authors: Xiao-Chi, Jia, Tor, Ny, Hsueh, Aaron J.W.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 1990; Elsevier
• Subjects: Androgen; Animals; Biological and medical sciences; Drug Synergism; Female; Fundamental and applied biological sciences. Psychology; Glucocorticoid; Glucocorticoids - administration & dosage; Granulosa cell, ovary; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Hormonal induction; Hormone metabolism and regulation; In Vitro Techniques; Mammalian female genital system; mRNA; Plasminogen activator activity; Protein Kinases - metabolism; Rats; Rats, Inbred Strains; RNA, Messenger - metabolism; Synergism; Testosterone Congeners - administration & dosage; Tissue Plasminogen Activator - biosynthesis; Tissue Plasminogen Activator - metabolism; Vertebrates: reproduction; Androgen; Plasminogen activator activity; Granulosa cell, ovary; mRNA; Glucocorticoid; Synergism; Hormonal induction; Cell culture; Rat; Enzyme; Rodentia; Gonadotropin RH; Plasminogen activator; Gene expression; Northern blotting; Ovary; Vertebrata; Mammalia; Epidermal growth factor; Messenger RNA; Enzymatic activity; Protein kinase; Female genital system; FSH; Granulosa; Sex steroid hormone
• ISSN: 0303-7207; 1872-8057; 1872-8057
• DOI: 10.1016/0303-7207(90)90187-D

Tissue-type plasminogen activator (tPA) is secreted by rat granulosa cells m response to treatment with activators of protein kinase A (follitropin, FSH), protein kinase C (gonadotropin-releasing hormone, GnRH) and tyrosine kinase (epidermal growth factor, EGF). Because steroid hormones have been shown to enhance the gonadotropin stimulation of ovarian differentiation, we investigated the effects of steroid hormones, alone or together with various kinase activators, on tPA activities and mRNA levels in cultured rat granulosa cells. Treatment of cells with dexamethasone (DEX; a glucocorticoid agonist) or R1881 (an androgen agonist) caused an increase in tPA secretion and mRNA levels. In addition, the stimulation of tPA activity and mRNA levels by FSH (50 ng/ml) was synergistically enhanced by cotreatment with DEX or R1881 in a time-dependent manner with 2.8- and 1.6-fold increase at 9 h after incubation as compared to cells treated with FSH alone. In contrast, treatment with diethylstilbestrol had no effect on tPA levels. Furthermore, tPA activity and mRNA levels induced by GnRH and EGF were also increased by cotreatment with DEX or R1881 as compared with cells treated with GnRH or EGF alone. Likewise, the stimulation of tPA mRNA levels by dibutyryl cAMP, a protein kinase A activator, and phorbol myristate acetate (PMA), a protein kinase C activator, was enhanced by cotreatment with DEX or R1881. These results demonstrate that glucocorticoid and androgen enhance tPA secretion and mRNA levels stimulated by FSH, GnRH and EGF in granulosa cells. The rat granulosa cells provide a useful model for studying the mechanism of regulation of tPA gene expression by steroid hormones.