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Cumulin and FSH Cooperate to Regulate Inhibin B and Activin B Production by Human Granulosa-Lutein Cells In Vitro.
Richani, Dulama; Constance, Katherine; Lien, Shelly; Agapiou, David; Stocker, William A; Hedger, Mark P; Ledger, William L; Thompson, Jeremy G; Robertson, David M; Mottershead, David G; Walton, Kelly L; Harrison, Craig A; Gilchrist, Robert B.
Afiliación
  • Richani D; Fertility & Research Centre, School of Women's and Children's Health, University of New South Wales Sydney, Kensington, New South Wales, Australia.
  • Constance K; Fertility & Research Centre, School of Women's and Children's Health, University of New South Wales Sydney, Kensington, New South Wales, Australia.
  • Lien S; Fertility & Research Centre, School of Women's and Children's Health, University of New South Wales Sydney, Kensington, New South Wales, Australia.
  • Agapiou D; Fertility & Research Centre, School of Women's and Children's Health, University of New South Wales Sydney, Kensington, New South Wales, Australia.
  • Stocker WA; Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
  • Hedger MP; Department of Chemistry and Biotechnology, Swinburne University of Technology, Hawthorn, Victoria, Australia.
  • Ledger WL; Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
  • Thompson JG; Fertility & Research Centre, School of Women's and Children's Health, University of New South Wales Sydney, Kensington, New South Wales, Australia.
  • Robertson DM; Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.
  • Mottershead DG; Fertility & Research Centre, School of Women's and Children's Health, University of New South Wales Sydney, Kensington, New South Wales, Australia.
  • Walton KL; Robinson Research Institute, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.
  • Harrison CA; Institute for Science and Technology in Medicine, School of Pharmacy, Keele University, Newcastle-under-Lyme, United Kingdom.
  • Gilchrist RB; Department of Physiology, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Endocrinology ; 160(4): 853-862, 2019 04 01.
Article en En | MEDLINE | ID: mdl-30753406
The oocyte-secreted factors bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) interact functionally, and it is hypothesized that this interaction may be mediated by formation of a GDF9:BMP15 heterodimer termed cumulin. GDF9 and BMP15 regulate folliculogenesis and ovulation rate and have been shown to regulate inhibin and activin, local regulators of folliculogenesis. The objective of this study was to determine whether cumulin regulates granulosa cell inhibin and activin production and whether this requires cooperation with FSH. Human granulosa-lutein (hGL) cells collected from patients undergoing in vitro fertilization were cultured with or without FSH with various forms of recombinant cumulin (native and cysteine mutants, with or without the prodomains), and cysteine mutant GDF9 or BMP15. Messenger RNA expression of the subunits of inhibins/activins (INHA, INHBA, INHBB) and secretion of inhibin A, inhibin B, and activin B were measured. Mature forms and proforms of cumulin stimulated comparable INHBB mRNA expression and secretion of inhibin B and activin B, whereas GDF9 or BMP15 exhibited no effect. Cumulin, but not GDF9 or BMP15, interacted synergistically with FSH to increase INHBB mRNA and inhibin B expression. FSH markedly stimulated INHA, which encodes the α subunit of inhibin A/B, and suppressed activin B. Cumulin with or without FSH did not significantly alter inhibin A. Together these data demonstrate that cumulin, but not GDF9 or BMP15, exerts paracrine control of FSH-induced regulation of inhibin B and activin B. The prodomains of cumulin may have a minimal role in its actions on granulosa cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oocitos / Activinas / Proteína Morfogenética Ósea 15 / Factor 9 de Diferenciación de Crecimiento / Hormona Folículo Estimulante / Inhibinas / Células Lúteas Límite: Female / Humans Idioma: En Revista: Endocrinology Año: 2019 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oocitos / Activinas / Proteína Morfogenética Ósea 15 / Factor 9 de Diferenciación de Crecimiento / Hormona Folículo Estimulante / Inhibinas / Células Lúteas Límite: Female / Humans Idioma: En Revista: Endocrinology Año: 2019 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Estados Unidos