Thyroid hormones affect the proliferation and/or mobilization of bulge stem cell population

Abstract

Thyroid hormones (TH) play a pivotal role in the development of mammalian skin, and are necessary for both the initiation and maintenance of hair growth. Adult hypothyroid rats showed impaired epidermal proliferation, hair growth and wound healing. Stem cells (SCs) located at the bulges of the hair follicles are responsible for hair cycling, and contribute to the regeneration of the new epidermis after wounding. Therefore a reduction in the number or function of bulge stem cells could be a cause of disturbed skin reepithelization and hair follicle maintenance. We hypothesized that a decrease in TH during prenatal development would affect the bulge stem cell population. Subclinical hypothyroidism was induced with propylthiouracil through drinking water in a dose of 1.5 mg/l in pregnant Albino Oxford rats, from the first day of gravidity and during lactation. The control group was untreated. Five, seven-day-old pups were euthanized and skin samples were taken from the dorsal part of their bodies. The number of hair follicles was estimated on an area of 1mm2 of dermis. For the immunohistochemical study, proliferating cell nuclear antigen (PCNA) (Santa Cruz Biotechnology) and NANOG (Thermo Scientific) antibodies were used. The number of PCNA and NANOG positive cells was estimated on the area of 1mm2 of hair follicle. The number of hair follicles was reduced and the expression of PCNA was decreased in the cells of the inner and outer sheath of hair follicles in the hypothyroid pups compared to the controls. They also had an increased number of NANOG positive bulge cells which we presume are multipotent SCs. Decreased expression of PCNA demonstrates low proliferation and increased expression of NANOG, which may be explained in two ways: 1) the inhibited differentiation of putative SCs and/or 2) the reduction of mobilization of these cells to the epidermis or sebaceous gland. Our results confirm that the lack of TH influences the formation of hair follicles in early infantile rat pups.