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Inhibin Binding Protein in Rats: Alternative Transcripts and Regulation in the Pituitary across the Estrous Cycle

Department of Neurobiology and Physiology (D.J.B., T.K.W.) Northwestern University and Department of Medicine (T.K.W.) Northwestern University Medical School Evanston, Illinois 60208-2850

Inhibin binding protein (InhBP) and the transforming growth factor-ß (TGFß) type III receptor, betaglycan, have been identified as putative inhibin 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 superfamily, as has been described for humans. Two abundant InhBP transcripts (4.4 and 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 isoform 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). InhBP-S does not contain a transmembrane domain and is predicted to be a soluble protein. Betaglycan was also detected in the pituitary; however, it was most abundant within the intermediate lobe. Although we also observed betaglycan immunopositive cells in the anterior pituitary, they rarely colocalized with FSHß-producing cells. We next examined physiological regulation of the coreceptors across the rat estrous cycle. Like circulating inhibin A and inhibin B levels, pituitary InhBP-L and InhBP-S mRNA levels were dynamically regulated across the cycle and were negatively correlated with serum FSH levels. Expression of both forms of InhBP was also positively correlated with serum inhibin B, but not inhibin A, levels. These data are particularly interesting in light of our in vitro observations that InhBP may function as an inhibin B-specific coreceptor. Pituitary betaglycan mRNA levels did not fluctuate across the cycle nor did they correlate with serum FSH. These observations, coupled with its pattern of expression within the pituitary, indicate that betaglycan likely functions as more than merely an inhibin 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 negative relation to serum FSH across the estrous cycle is an important step in this direction.

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