Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/120608
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Type: Journal article
Title: Cumulin and FSH cooperate to regulate inhibin B and activin B production by human granulosa-lutein cells In vitro
Author: Richani, D.
Constance, K.
Lien, S.
Agapiou, D.
Stocker, W.A.
Hedger, M.P.
Ledger, W.L.
Thompson, J.G.
Robertson, D.M.
Mottershead, D.G.
Walton, K.L.
Harrison, C.A.
Gilchrist, R.B.
Citation: Endocrinology, 2019; 160(4):853-862
Publisher: Oxford Academic
Issue Date: 2019
ISSN: 0013-7227
1945-7170
Statement of
Responsibility: 
Dulama Richani, Katherine Constance, Shelly Lien, David Agapiou, William A. Stocker, Mark P. Hedger, William L. Ledger, Jeremy G. Thompson, David M. Robertson, David G. Mottershead, Kelly L. Walton, Craig A. Harrison and Robert B. Gilchrist
Abstract: 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.
Keywords: Activins; Bone Morphogenetic Protein 15; Chorionic Gonadotropin; Female; Follicle Stimulating Hormone; Growth Differentiation Factor 9; Humans; Inhibins; Luteal Cells; Oocyte Retrieval; Oocytes; Signal Transduction
Rights: © 2019 Endocrine Society.
RMID: 0030108338
DOI: 10.1210/en.2018-01026
Appears in Collections:Agriculture, Food and Wine publications

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