S

Mullerian Inhibitory Factor (MIF)

Precursor/Activin Form (?)

57 kDa

12.5 kDa

Mature MIF 12.5 kDa

2. Inhibin

The regulation of secretion of FSH from the adenohypophysis is only partly dependent on gonadal steroids; in addition, the protein hormone inhibin acts principally at the level of the pituitary to diminish the secretion of FSH. Inhibin is a hormone secreted in males by the Sertoli cells and in females by the ovarian follicles.

Inhibin is a heterodimeric protein; it has a common a-subunit and one of two /3-subunits. Thus, there are two isoforms of inhibins, either inhibin A (a/3A) or inhibin B (a/3B) (see Figure 12-6). The /3-subunit is 18 kDa and the a-subunit is 14 kDa. Structurally the inhibins belong to the transforming growth factor (TGF-)3) multigene family (see Chapter 19). The a-and /3-subunits are cross-linked by one or more disulfide bridges. As yet, it is not known whether the detailed structures of male- and female-derived inhibins are identical.

The structure of the inhibins is also related to that of another peptide hormone, the activins (see the following). Figure 12-6 compares the structures of inhibins and activins.

Both subunits of mature inhibin are derived from precursor prohormone species. Thus, the a-subunit's primary transcript contains 364 amino acids, while the jS-subunit's primary transcript contains 424 amino 140 kDa acids. Both the mature a- and /3-subunits lie at the extreme carboxyl end of their respective prohormone species. Each mature subunit is preceded by either two a-subunit or five /8-subunit arginines, which constitute the cleavage sites for proteolytic release of the mature subunits. It is known that the a- and /3-subunits of biologically active inhibin are linked by disulfide

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