Growth Differentiation Factor 9 (GDF9) Stimulates Proliferation and Inhibits Steroidogenesis by Bovine Theca Cells: Influence of Follicle Size on Responses to GDF91
Growth Differentiation Factor 9 (GDF9) Stimulates Proliferation and Inhibits Steroidogenesis by Bovine Theca Cells: Influence of Follicle Size on Responses to GDF91
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生长分化因子 9 (GDF9) 刺激牛膜细胞增殖并抑制类固醇生成：卵泡大小对 GDF91 反应的影响
作者：
L. Spicer;P. Aad;D. Allen;S. Mazerbourg;A. Payne;A. Hsueh
摘要卵巢卵泡发育受多种旁分泌和内分泌调节因子的控制，包括卵母细胞源性生长分化因子9（GDF 9）和生物可利用的胰岛素样生长因子1（IGF 1）的局部增加。研究了GDF 9对从小（3-6 mm）和大（8-22 mm）卵泡收集的卵泡膜细胞功能的影响。在LH和IGF 1存在下培养的小卵泡膜细胞中，GDF 9增加了细胞数量和DNA合成，通过3 H-胸苷掺入试验测定，并剂量依赖性地降低孕酮和雄烯二酮的产生。在IGF 1诱导的细胞增殖或类固醇产生方面，来自大卵泡的卵泡膜细胞对GDF 9几乎没有反应或没有反应。小卵泡膜细胞研究表明，GDF 9降低了卵泡膜细胞中LHR和CYP 11 A1 mRNA的丰度，但对IGF 1 R、星星或CYP 17 A1 mRNA丰度或CYP 17 A1蛋白染色的细胞百分比没有影响。在转染的卵泡膜细胞中，GDF 9类似于母体针对十肢瘫痪（SMAD）2/3诱导的CAGA启动子活性而活化。小卵泡膜细胞比大卵泡膜细胞有更多的ALK 5 mRNA。小卵泡颗粒细胞似乎比大卵泡颗粒细胞具有更高的GDF 9 mRNA丰度，但卵泡膜细胞没有检测到GDF 9 mRNA。我们的结论是，卵泡膜细胞从小卵泡GDF 9比那些从大卵泡和GDF 9 mRNA可能产生的颗粒细胞在牛。由于GDF 9增加了卵泡膜细胞增殖并降低了卵泡膜细胞类固醇生成，因此卵母细胞和颗粒细胞衍生的GDF 9可以同时促进卵泡膜细胞增殖并防止卵泡内膜在早期卵泡发育期间过早分化。
Abstract Ovarian follicular development is controlled by numerous paracrine and endocrine regulators, including oocyte-derived growth differentiation factor 9 (GDF9), and a localized increase in bioavailable insulin-like growth factor 1 (IGF1). The effects of GDF9 on function of theca cells collected from small (3–6 mm) and large (8–22 mm) ovarian follicles were investigated. In small-follicle theca cells cultured in the presence of both LH and IGF1, GDF9 increased cell numbers and DNA synthesis, as measured by a 3H-thymidine incorporation assay, and dose-dependently decreased both progesterone and androstenedione production. Theca cells from large follicles had little or no response to GDF9 in terms of cell proliferation or steroid production induced by IGF1. Small-follicle theca cell studies indicated that GDF9 decreased the abundance of LHR and CYP11A1 mRNA in theca cells, but had no effect on IGF1R, STAR, or CYP17A1 mRNA abundance or the percentage of cells staining for CYP17A1 proteins. GDF9 activated similar to mothers against decapentaplegics (SMAD) 2/3-induced CAGA promoter activity in transfected theca cells. Small-follicle theca cells had more ALK5 mRNA than large-follicle theca cells. Small-follicle granulosa cells appeared to have greater GDF9 mRNA abundance than large-follicle granulosa cells, but theca cells had no detectable GDF9 mRNA. We conclude that theca cells from small follicles are more responsive to GDF9 than those from large follicles and that GDF9 mRNA may be produced by granulosa cells in cattle. Because GDF9 increased theca cell proliferation and decreased theca cell steroidogenesis, oocyte- and granulosa cell-derived GDF9 may simultaneously promote theca cell proliferation and prevent premature differentiation of the theca interna during early follicle development.
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DOI：
10.1073/pnas.180295197
发表时间：
2000-08-29
影响因子：
11.1
作者：
Elvin, JA;Yan, CN;Matzuk, MM
通讯作者：
Matzuk, MM
影响因子：
--
作者：
Julia A. Elvin;Amander T. Clark;Pei Wang;N. Wolfman;M. Matzuk
通讯作者：
Julia A. Elvin;Amander T. Clark;Pei Wang;N. Wolfman;M. Matzuk
生长分化因子 9 抑制人颗粒细胞和卵泡膜细胞中 35-单磷酸腺苷刺激的类固醇生成。
DOI：
10.1210/jcem.87.6.8551
发表时间：
2002
期刊：
The Journal of clinical endocrinology and metabolism.
影响因子：
--
作者：
Yamamoto,Noriko;Christenson,LaneK;McAllister,JanM;Strauss3rd,JeromeF
通讯作者：
Strauss3rd,JeromeF
影响因子：
4.8
作者：
ROBERTS, AJ;SKINNER, MK
通讯作者：
SKINNER, MK
影响因子：
--
作者：
J. Elvin;Changning Yan;Pei Wang;K. Nishimori;M. Matzuk
通讯作者：
J. Elvin;Changning Yan;Pei Wang;K. Nishimori;M. Matzuk