ERβ Regulation of Gonadotropin Responses during Folliculogenesis
Gonadotropins are essential for regulating ovarian development, steroidogenesis, and gametogenesis. While follicle stimulating hormone (FSH) promotes the development of ovarian follicles, luteinizing hormone (LH) regulates preovulatory maturation of oocytes, ovulation, and formation of corpus luteum...
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10348 |
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| author | Eun B. Lee V. Praveen Chakravarthi Michael W. Wolfe M. A. Karim Rumi |
| author_facet | Eun B. Lee V. Praveen Chakravarthi Michael W. Wolfe M. A. Karim Rumi |
| author_sort | Eun B. Lee |
| collection | DOAJ |
| description | Gonadotropins are essential for regulating ovarian development, steroidogenesis, and gametogenesis. While follicle stimulating hormone (FSH) promotes the development of ovarian follicles, luteinizing hormone (LH) regulates preovulatory maturation of oocytes, ovulation, and formation of corpus luteum. Cognate receptors of FSH and LH are G-protein coupled receptors that predominantly signal through cAMP-dependent and cAMP-independent mechanisms that activate protein kinases. Subsequent vital steps in response to gonadotropins are mediated through activation or inhibition of transcription factors required for follicular gene expression. Estrogen receptors, classical ligand-activated transcriptional regulators, play crucial roles in regulating gonadotropin secretion from the hypothalamic–pituitary axis as well as gonadotropin function in the target organs. In this review, we discuss the role of estrogen receptor β (ERβ) regulating gonadotropin response during folliculogenesis. Ovarian follicles in Erβ knockout (Erβ<sup>KO</sup>) mutant female mice and rats cannot develop beyond the antral state, lack oocyte maturation, and fail to ovulate. Theca cells (TCs) in ovarian follicles express LH receptor, whereas granulosa cells (GCs) express both FSH receptor (FSHR) and LH receptor (LHCGR). As oocytes do not express the gonadotropin receptors, the somatic cells play a crucial role during gonadotropin induced oocyte maturation. Somatic cells also express high levels of estrogen receptors; while TCs express ERα and are involved in steroidogenesis, GCs express ERβ and are involved in both steroidogenesis and folliculogenesis. GCs are the primary site of ERβ-regulated gene expression. We observed that a subset of gonadotropin-induced genes in GCs, which are essential for ovarian follicle development, oocyte maturation and ovulation, are dependent on ERβ. Thus, ERβ plays a vital role in regulating the gonadotropin responses in ovary. |
| first_indexed | 2024-03-10T07:00:21Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:00:21Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e741c2199988490385412131aa32b8f12023-11-22T16:08:14ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191034810.3390/ijms221910348ERβ Regulation of Gonadotropin Responses during FolliculogenesisEun B. Lee0V. Praveen Chakravarthi1Michael W. Wolfe2M. A. Karim Rumi3Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USADepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USADepartment of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USADepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USAGonadotropins are essential for regulating ovarian development, steroidogenesis, and gametogenesis. While follicle stimulating hormone (FSH) promotes the development of ovarian follicles, luteinizing hormone (LH) regulates preovulatory maturation of oocytes, ovulation, and formation of corpus luteum. Cognate receptors of FSH and LH are G-protein coupled receptors that predominantly signal through cAMP-dependent and cAMP-independent mechanisms that activate protein kinases. Subsequent vital steps in response to gonadotropins are mediated through activation or inhibition of transcription factors required for follicular gene expression. Estrogen receptors, classical ligand-activated transcriptional regulators, play crucial roles in regulating gonadotropin secretion from the hypothalamic–pituitary axis as well as gonadotropin function in the target organs. In this review, we discuss the role of estrogen receptor β (ERβ) regulating gonadotropin response during folliculogenesis. Ovarian follicles in Erβ knockout (Erβ<sup>KO</sup>) mutant female mice and rats cannot develop beyond the antral state, lack oocyte maturation, and fail to ovulate. Theca cells (TCs) in ovarian follicles express LH receptor, whereas granulosa cells (GCs) express both FSH receptor (FSHR) and LH receptor (LHCGR). As oocytes do not express the gonadotropin receptors, the somatic cells play a crucial role during gonadotropin induced oocyte maturation. Somatic cells also express high levels of estrogen receptors; while TCs express ERα and are involved in steroidogenesis, GCs express ERβ and are involved in both steroidogenesis and folliculogenesis. GCs are the primary site of ERβ-regulated gene expression. We observed that a subset of gonadotropin-induced genes in GCs, which are essential for ovarian follicle development, oocyte maturation and ovulation, are dependent on ERβ. Thus, ERβ plays a vital role in regulating the gonadotropin responses in ovary.https://www.mdpi.com/1422-0067/22/19/10348estrogen receptor βfollicle stimulating hormoneluteinizing hormonesteroidogenesisfollicle developmentoocyte maturation |
| spellingShingle | Eun B. Lee V. Praveen Chakravarthi Michael W. Wolfe M. A. Karim Rumi ERβ Regulation of Gonadotropin Responses during Folliculogenesis International Journal of Molecular Sciences estrogen receptor β follicle stimulating hormone luteinizing hormone steroidogenesis follicle development oocyte maturation |
| title | ERβ Regulation of Gonadotropin Responses during Folliculogenesis |
| title_full | ERβ Regulation of Gonadotropin Responses during Folliculogenesis |
| title_fullStr | ERβ Regulation of Gonadotropin Responses during Folliculogenesis |
| title_full_unstemmed | ERβ Regulation of Gonadotropin Responses during Folliculogenesis |
| title_short | ERβ Regulation of Gonadotropin Responses during Folliculogenesis |
| title_sort | erβ regulation of gonadotropin responses during folliculogenesis |
| topic | estrogen receptor β follicle stimulating hormone luteinizing hormone steroidogenesis follicle development oocyte maturation |
| url | https://www.mdpi.com/1422-0067/22/19/10348 |
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