Cell-Cycle Inhibitors p27Kip1 and p21Cip1 Regulate Murine Sertoli Cell Proliferation1
- 1 June 2005
- journal article
- Published by Oxford University Press (OUP) in Biology of Reproduction
- Vol. 72 (6), 1429-1436
- https://doi.org/10.1095/biolreprod.105.040386
Abstract
Thyroid hormone inhibits neonatal Sertoli cell proliferation and recent results have shown that thyroid hormone upregulates cyclin-dependent kinase inhibitors (CDKIs) p27Kip1 and p21Cip1 (also known as CDKN1B and CDKN1A, respectively) in neonatal Sertoli cells. This suggests that these CDKIs, which negatively regulate the cell cycle, could be critical in Sertoli cell proliferation. Consistent with this hypothesis, mice lacking p27Kip1 develop testicular organomegaly, but Sertoli cell numbers have not been determined. Likewise, effects of loss of p21Cip1 or both p27 and p21 on Sertoli cell number and testicular development were unknown. To determine if p27 and/or p21 regulate Sertoli cell proliferation, we measured Sertoli cell proliferation at Postnatal Day 16 and testis weight, Sertoli cell number, and daily sperm production (DSP) in 4-mo-old wild-type (WT), p21 knockout (p21KO), p27 knockout (p27KO), and p27/p21 double-knockout (DBKO) mice. Testis weights were increased 27%, 42%, and 86% in adult p21KO, p27KO, and DBKO mice, respectively, compared with WT. Sertoli cell number also was increased 48%, 126%, and 126% in p21KO, p27KO, and DBKO mice, respectively, versus WT. DSP in p21KO, p27KO, and DBKO testes also showed significant increases compared with WT mice. Although DSP was increased, there were increased spermatogenic defects observed in both p27KO and DBKO mice compared with WT. These data indicate that both p27 and p21 play an inhibitory role in regulating adult Sertoli cell number such that loss of either CDKI produces primary increases in Sertoli cell number and secondary increases in DSP and testis weight. Furthermore, loss of both CDKIs causes additive effects on DSP and testis weight, suggesting a central role for these CDKIs in testis development.This publication has 38 references indexed in Scilit:
- Loss of cyclin‐dependent kinase inhibitors produces adipocyte hyperplasia and obesityThe FASEB Journal, 2004
- Association between Insulin-Like Growth Factor-ICancer Epidemiology, Biomarkers & Prevention, 2004
- The Cyclin-dependent Kinase Inhibitors p27Kip1 and p21Cip1 Cooperate to Restrict Proliferative Life Span in Differentiating Ovarian CellsPublished by Elsevier BV ,2003
- Testis Morphometry, Seminiferous Epithelium Cycle Length, and Daily Sperm Production in Domestic Cats (Felis catus)Biology of Reproduction, 2003
- A Syndrome of Multiorgan Hyperplasia with Features of Gigantism, Tumorigenesis, and Female Sterility in p27Kip1-Deficient MiceCell, 1996
- Enhanced Growth of Mice Lacking the Cyclin-Dependent Kinase Inhibitor Function of p27Kip1Cell, 1996
- Mice Lacking p27Kip1 Display Increased Body Size, Multiple Organ Hyperplasia, Retinal Dysplasia, and Pituitary TumorsCell, 1996
- Triiodothyronine Inhibits Proliferation and Stimulates Differentiation of Cultured Neonatal Sertoli Cells: Possible Mechanism for Increased Adult Testis Weight and Sperm Production Induced by Neonatal Goitrogen Treatment1Biology of Reproduction, 1994
- Effects of Testosterone on Spermatogenic Cell Populations in the Adult Rat1Biology of Reproduction, 1994
- Stimulation by follicle-stimulating hormone of DNA synthesis and of mitosis in cultured Sertoli cells prepared from testes of immature ratsMolecular and Cellular Endocrinology, 1977