LOCALIZATION OF INSULIN-LIKE-GROWTH-FACTOR RECEPTORS IN SKIN FOLLICLES OF SHEEP (OVIS-ARIES) AND CHANGES DURING AN INDUCED GROWTH-CYCLE

Pelage growth cycles are regulated by circulating prolactin in many ma mmals, but the intercellular mediators of this signaling are unknown. Binding sites for insulin-like growth factors (IGFs) were examined in sheep skin to show changes in distribution and abundance of IGF recept ors associated with a prolactin stimulus and the subsequent hair folli cle growth cycle. Follicle cycles were induced in New Zealand Wiltshir e ewes by a surge in plasma prolactin following a 4-month period of pr olactin suppression with bromocriptine. Eight treated and three contro l sheep were slaughtered at intervals over 43 days during the follicle growth cycle. At 12-20 days after the elevation of prolactin, wool fo llicles passed through brief catagen and telogen phases, followed by a return to anagen. IGF binding sites were localized in skin sections b y incubation with I-125-IGF-I or I-125-IGF-II. Displacement with compe titive binding inhibitors (unlabeled IGF-I, IGF-II, des(1-3)IGF-I, des (1-6)IGF-II, or insulin) and affinity cross-linking showed that these binding sites were predominantly IGF type 1 and type 2 (mannose-6-phos phate) receptors. The radioligands bound especially to follicle germin al cells and prekeratinocytes. Increases in specific binding of both r adioligands were observed after the rise in prolactin, but prior to an atomical changes in follicles associated with cessation of growth. For IGF-I, highest binding density was observed during catagen in the ger minal matrix and dermal papilla cells. For IGF-II, peak density occurr ed during late anagen/early catagen in the germinal matrix and during telogen in the dermal papilla. These cycle associated changes in recep tor availability suggest that IGF receptors are involved in control of the wool growth. (C) 1997 Elsevier Science Inc.