NEONATAL-HYPOTHYROIDISM CAUSES DELAYED SERTOLI-CELL MATURATION IN RATS TREATED WITH PROPYLTHIOURACIL - EVIDENCE THAT THE SERTOLI-CELL CONTROLS TESTIS GROWTH

Background: The testes of rats treated neonatally with propylthiouraci l (PTU) grow to almost twice their normal size, The cause of testicula r enlargement has been suggested to be the result of delayed maturatio n of Sertoli cells, allowing Sertoli cell division to occur beyond the 15th postnatal. day, the commonly recognized cutoff date for Sertoli cell divisions, It has been shown that an increased population of Sert oli cells in postnatal development supports increased numbers of germ cells in adult animals, After examining developing rats treated neonat ally with PTU, we hypothesized that an approximate 10-day delay in mat uration was occurring and proceeded to test this hypothesis experiment ally, Thus the purpose of this report was to determine if a 10-day del ay in maturation could explain the increased numbers of Sertoli cells and increased testis size in PTU-treated animals. Methods: Both contro l animals and animals treated neonatally with PTU N = 5/group were sac rificed at 15 and 25 days of age and prepared for electron microscopy. Results: Micrographs show and morphometric ultrastructural analysis o f numerous parameters demonstrated at the 95% probability level that S ertoli cells from 25-day-old PTU animals are not different in size and most constituents (volume and surface area) from 15-day-old control a nimals and are less mature than 25-day-old control animals, Mitosis of Sertoli cells was observed in PTU-treated animals in 25-day-old anima ls but not in age-matched controls, The number of Sertoli cells in 25- day-old PTU-treated animals is significantly increased over age-matche d controls, Micrographs show the presence of immature Sertoli cell nuc lei in 25-day-old animals receiving PTU as well as increased germ cell degeneration in this group, Sertoli cell tight junction formation is also delayed in PTU-treated animals as compared with controls. Conclus ions: Together, the data show that delayed maturation of Sertoli cells occurs in treated animals that corresponds to a minimum of 10 develop mental days, In the immature state, Sertoli cells continue to divide, Data presented herein and published data related to PTU treatment indi cate that delayed maturation of the Sertoli cell results in delayed ma turation and proliferation of other testicular cell types, From this a nd from published data, the hypothesis is presented that the Sertoli c ell is responsible for the overall control of testis development. (C) 1995 Wiley-Liss, Inc.