Inhibin binding protein in rats: Alternative transcripts and regulation inthe pituitary across the estrous cycle

Inhibin binding protein (InhBP) and the transforming growth factor-beta (TG F beta) type III receptor, betaglycan, have been identified as putative inh ibin coreceptors. Here we cloned the InhBP cDNA in rats and predict that it encodes a large membrane-spanning protein that is part of the Ig superfami ly, as has been described for humans. Two abundant InhBP transcripts (4.4 a nd 1.8 kb) were detected in the adult rat pituitary. The larger transcript encodes the full-length protein while the 1.8-kb transcript (InhBP-short or InhBP-S) corresponds to a splice variant of the receptor. This truncated i soform contains only the N-terminal signal peptide and first two (of 12) Ig -like domains observed in the full-length InhBP (InhBP-long or InhBP-L). In hBP-S does not contain a transmembrane domain and is predicted to be a solu ble protein. Betaglycan was also detected in the pituitary; however, it was most abundant within the intermediate lobe. Although we also observed beta glycan immunopositive cells in the anterior pituitary, they rarely colocali zed with FSH beta -producing cells. We next examined physiological regulati on of the coreceptors across the rat estrous cycle. Like circulating inhibi n A and inhibin B levels, pituitary InhBP-L and InhBP-S mRNA levels were dy namically regulated across the cycle and were negatively correlated with se rum FSH levels. Expression of both forms of InhBP was also positively corre lated with serum inhibin B, but not inhibin A, levels. These data are parti cularly interesting in light of our in vitro observations that InhBP may fu nction as an inhibin B-specific coreceptor. Pituitary betaglycan mRNA level s did not fluctuate across the cycle nor did they correlate with serum FSH. These observations, coupled with its pattern of expression within the pitu itary, indicate that betaglycan likely functions as more than merely an inh ibin coreceptor within the pituitary. A direct role for InhBP or betaglycan in regulation of pituitary FSH by inhibin in vivo has yet to be determined , but the demonstration of dynamic regulation of pituitary InhBP and its ne gative relation to serum FSH across the estrous cycle is an important step in this direction.