Mode of action of mouse epidermal growth factor on the wool follicles of Merino sheep: an ultrastructural study

Abstract

The follicular mechanisms involved in and associated with the depilatory action of infused mouse epidermal growth factor (mEGF) on wool follicles were investigated ultrastructurally in the course of research into biological wool harvesting as an alternative to conventional shearing. Ultrastructural alterations observed during mEGF-induced follicle involution indicated three separate follicular responses to mEGF. (i) Catagenic regression lasting 4 days occurred in all follicles. This process initially (at 1 day) involved decline in cellular proliferation in the follicle bulbs, decline in the formation of precursor structural proteins in inner root sheath (IRS) and fibre cells and a delay in their hardening, and deletion of cells by apoptosis. Synthesis of precursor proteins subsequently ceased in a proportion of the follicles at 2 days, culminating in the formation of tapered fibre ends at 4 days. Regeneration of these follicles commenced at 4-6 days. Fibre production continued in the remaining follicles, though on a much reduced scale, resulting in the formation of transiently thinned fibres. (ii) Disruptive lesions formed in IRS and fibre cells in the keratogenous zone of all follicles during infusion. Their formation involved initial dilatation and vesiculation of endoplasrnic reticulum and mitochondria1 swelling, evident as early as 1 h, and subsequent intercellular accumulation of flocculent material within 12 h, indicative of abnormal fluid transport. (iii) The sebaceous glands underwent transient hypcrplasia involving extensive deposition of glycogen at 2 days, before returning to normal by 4-6 days through apoptosis. These follicular responses demonstrate two diverse modes of action of mEGF infusion on the wool follicles: a quasi-physiological, catagenic, inhibitory action on fibre growth, resembling in part catagen of cyclic hair growth, thereby culminating in a fleece 'break' and/or fleece shedding, and an apparently unrelated pathological action on differentiating IRS and fibre cells and undifferentiated sebaceous cells.