Ontogeny of the response to thyroxine (T4) in the porcine fetus: interrelationships between serum T4, serum insulin-like growth factor-1 (IGF-1) and differentiation of skin and several adipose tissues.

The temporal aspect of thyroxine (T4) enhanced development of several fetal adipose tissue depots (locations) and skin was examined in the present study. On day 70 of gestation pig fetuses were either hypophysectomized (hypox), hypoxed and implanted with T4 pellets or left intact (control). Subsequently, fetuses were removed for study at either 73, 75, 80, 85 and 90 days of gestation. Serum levels of T4 and insulin-like growth factor I (IGF-I) were significantly elevated by T4 after 3 days of treatment and throughout the study. T4 treatment enhanced development of skin, inner and outer subcutaneous (SQ) adipose tissue and adipocyte lobules around hair follicles (HFL's) but degree of response and response time were tissue or depot dependent. The T4 response time was shortest for skin and HFL's, longest for inner SQ and intermediate for the outer SQ. Considering the entire treatment period, magnitude of the T4 response was much greater for skin and HFL's than for outer and inner SQ tissues. Possibly, these developmental characteristics indicate that T4 directly influences skin and HFL's and indirectly influences inner SQ adipose tissue by increasing production of a locally produced adipogenic growth factor. Furthermore, developmental characteristics (morphological) indicated that putative local growth factor mediation of T4 action may depend on stage of development or maturity of the tissue. IGF-I is clearly the most logical candidate as a putative local mediator of T4, but evidence at the molecular level is needed to prove this suggestion. Regardless, the particular adipose tissue location or depot is an important aspect of hormone responsiveness during the critical or sensitive period of fetal adipose tissue development.