title: Effects of 3, 5, 3'-triiodothyronine (t3) and follicle stimulating hormone on apoptosis and proliferation of rat ovarian granulosa cells.
abstract: Thyroid hormone (TH) is important for normal reproductive functions and dysregulation of TH support is associated with reproductive disorders. We have previously reported that 3,5,3'-triiodothyronine (T₃) increases follicle stimulating hormone (FSH)-induced preantral follicle growth in vitro. Interaction of hormones with apoptosis and proliferation of granulosa cells is poorly understood. The present study investigated the role and the mechanism of T₃ and/or FSH on granulosa cell apoptosis and proliferation. Granulosa cells harvested from DES-primed immature rats were exposed to T₃ (1 nM) and/or FSH (100 ng/ml) for 24-48 h. We demonstrated by TUNEL assays that the hormones prevented cells from C8-ceramide-induced apoptosis. The Src/PI3K/Akt pathway was involved in the regulation of granulosa cell survival. While ineffective alone, T₃ significantly enhanced the proliferating cell nuclear antigen (PCNA) content of FSH-induced granulosa cells, consistent with the cell number pattern after treatment. Moreover, the action of the hormones on cell proliferation was also shown to be mediated by the Src/PI3K/Akt pathway. Taken together, these results suggest that T₃ potentiates the cell survival action of FSH through inhibiting cell apoptosis and promoting cell proliferation. Moreover, the protective and survival effects of hormones are mediated by the activation of Src/PI3K/Akt pathway.
authors.affiliation: College of Life Science, Capital Normal University, Beijing 100048, People's Republic of China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.forename: Baochang
authors.initials: B
authors.lastname: Zhu
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.forename: Shangyu
authors.initials: S
authors.lastname: Yu
authors.forename: Na
authors.initials: N
authors.lastname: An
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005640:Follicle Stimulating Hormone / Q000502:physiology*; D006107:Granulosa Cells / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013110:Sphingosine / Q000031:analogs & derivatives; D014284:Triiodothyronine / Q000502:physiology*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C066099:2,3-N-octanoylsphingosine; D014284:Triiodothyronine; D005640:Follicle Stimulating Hormone; D019869:Phosphatidylinositol 3-Kinases; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D013110:Sphingosine