FSH stimulates the expression of the ADAMTS-16 protease in mature human ovarian follicles

We report the characterization of full-length human ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs)-16, a novel member of the disintegrin and metalloproteinase with thrombospondin motifs (hence ADAMTS) family. ADAMTS-16 is highly expressed both in the kidney and in the ovary, where it is predominantly expressed in the parietal granulosa cells of pre-ovulatory follicles but only slightly expressed in cells of the cumulus oophorus. In fully differentiated luteinizing granulosa cells, follicle-stimulating hormone and forskolin induces expression of ADAMTS-16, suggesting that it is regulated via the cAMP pathway. Luteinizing hormone had a minor effect on the expression of ADAMTS-16. ADAMTS-16 is capable of cleaving alpha2-macroglobulin (MG), a common substrate for proteases, which is present at high concentrations in the follicular fluid of ovarian follicles. These studies provide the first evidence that ADAMTS-16 is an active protease and suggest a physiological role of ADAMTS-16 in ovarian follicles, at least during the pre-ovulatory phase.