466 PIERCE & PARSONS lutropin [luteinizing hormone (LH) or interstitial cell-stimulating hormone] and follitropin [follicle-stimulating hormone (FSH)]. Their general biologi cal roles are the stimulation of testicular and ovarian functions via the regulation of gametogenesis and steroid hormone synthesis in the gonads (1). Pituitary thyroid-stimulating hormone (thyrotropin or TSH) regulates a wide variety of biochemical and physiological processes in the thyroid that result in the synthesis and secretion of thyroid hormones (2). The most studied glycoprotein hormone of placental origin is human chorionic gonadotropin (heG); its hormonal effects closely resemble those of pitui tary LH. These hormones, with their diverse physiological functions, are closely related in structure and are the most complex protein hormones yet recognized. Each consists of two peptide chains or subunits, designated a and f3. Both subunits are glycosylated at specific residues and are highly cross-linked internally by disulfide bonds. These hormones are found in all mammals studied, and hormones with similar properties have also been observed in lower vertebrates including teleost fishes (3-5). Hormonal activ ity is expressed only after strong and specific noncovalent interactions between an a and a f3 subunit. Within a species, the a sequence is essentially identical for each hormone; it also is highly conserved from species to species. Both inter hormone and interspecies hybrid hormones can be pre pared. The hormonal activity of such hybrids is always dictated by the particular f3 subunit present, though how its specificity is expressed is not clear. The f3 subunits also show considerable homology in structure; it is most probable that they evolved from a common precursor (6). The hor mones elicit their biological responses after interaction with a receptor or receptors on the surface of target cells, presumably by stimulation of the synthesis of cAMP with subsequent effects on the activity of various protein kinases. The identities of specific substrates for the kinases in the case of each hormone are still largely uncertain. The chemistry of the interaction of these hormones with their receptors is of particular interest because, as far as protein and peptide hormones are concerned, their subunit structure is unique, with the exact role of the common, a subunit unknown. Studies on chemically and enzymatically modified hormones provide considerable evidence that regions of the a subunit, most probably in concert with domains on the f3 subunit, are involved directly in recognition of receptors. Each subunit is apparently produced by a separate gene, and cell-free translation of enriched mRNAs gives rise to products that can be precipitated with antisera specific to one or the other subunit. As with other secretory proteins, the translated mes sage includes a leader or signal peptide that is removed by processing. Little is known about mechanisms of control in the biosynthesis of individual subunits or how an a and f3 subunit assemble, in vivo, to yield active