Equine granulosa-theca cell tumors express inhibin alpha- and beta A-subunit messenger ribonucleic acids and proteins.
The association of equine granulosa-theca cell tumors with atrophied contralateral ovaries and abnormal estrous cycles suggests that these tumors produce hormones that affect pituitary gonadotropin production. Because inhibin, a heterodimer protein secreted by granulosa cells, decreases FSH production, we examined the presence of inhibin alpha- and beta A-subunits and their mRNAs in ovarian tumors obtained from three mares. These tumors contained neoplastic cords and nodules, multiple fluid-filled cysts, and a predominance of neoplastic granulosa cells. Reduced proteins from tumor-conditioned media were analyzed by electrophoresis and immunoblotting using antibodies directed against peptide fragments of the alpha- and beta A-chains of porcine inhibin. Specific bands at 50-kDa and 36-kDa for the inhibin alpha-subunit and at 44 kDa and 13 kDa for the inhibin beta A-subunit were observed in these tumors. Northern blot hybridization of 32P-labeled rat inhibin alpha- and beta A-subunit complementary RNAs to total RNA from each tumor revealed predominant bands of activity in all three tumors at 1.5 and 7 kb for the alpha- and beta A-subunit mRNAs, respectively. These results demonstrate that equine granulosa-theca cell tumors express the mRNAs for inhibin alpha- and beta A-subunits and also secrete inhibin subunits that could potentially affect gonadotropin production in afflicted mares. Furthermore, cells derived from these tumors may provide a useful model for understanding inhibin gene regulation and ovarian tumorigenesis.
Piquette
G N
GN
Department of Reproductive Medicine, University of California, San Diego, La Jolla 92093.
Kenney
R M
RM
Sertich
P L
PL
Yamoto
M
M
Hsueh
A J
AJ
D000818:Animals; D005260:Female; D006106:Granulosa Cell Tumor / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D006734:Horse Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006736:Horses; D007265:Inhibins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013798:Thecoma / Q000235:genetics / Q000378:metabolism / Q000662:veterinary*
D012333:RNA, Messenger; D007265:Inhibins