Endocrine Abstracts

Theca cells are indispensable for female reproduction being the source of androgens required for follicular oestrogen synthesis and also for interacting with androgen receptors in the ovary and other somatic tissues. Differentiated theca interna cells acquire responsiveness to LH and other endocrine signals, including insulin, that upregulate the steroidogenic pathway leading to androgen biosynthesis. In addition, numerous intraovarian factors of thecal, granulosal and/or oocyte origin modulate thecal androgen production, mostly in an inhibitory manner; many of these are members of the TGF-β family. These ligands bind to different combinations of type-I and -II signalling receptors expressed by theca cells; ligand-receptor interaction is regulated by various extracellular binding proteins, co-receptors and likely by competition amongst cross-reactive ligands for common receptors. In vitro studies in the author’s and other laboratories indicate functional redundancy amongst TGF-β family ligands in that activins and various BMPs (including BMP2, 4, 6, 7) suppress thecal androgen production in an inhibin-reversible manner. Follistatins neutralize activin action while other binding proteins (e.g. noggin, gremlin) selectively neutralize different BMPs. Other ligands including TGF-β_{1, 2, 3} also strongly inhibit thecal androgen production while AMH and GDF9 appear to have limited effect. Recent evidence indicates that myostatin (GDF8) is expressed within human and bovine follicles and suppresses thecal androgen production in a manner opposed by follistatin. It has also emerged that bovine theca cells express free inhibin-α subunit and that its knockdown suppresses androgen output although the significance of this finding requires further investigation. With regard to ovarian hyperandrogenaemia commonly associated with polycystic ovarian syndrome, it is hypothesised that this could be due to compromised intraovarian signalling by one or more TGF-β family ligands that tonically suppress thecal androgen synthesis. This could arise from altered expression or processing of ligands, antagonists (i.e. inhibins), extracellular binding proteins, signalling receptors, co-receptors and/or intracellular signal transduction components.