Effects of growth differentiation factor 8 on steroidogenesis in human granulosa lutein cells

Capsule:
Growth differentiation factor 8 increased estradiol production by up-regulating the aromatase and follicle-stimulating hormone receptor, but decreased progesterone production by down-regulating steroidogenic acute regulatory protein and luteinizing hormone receptors in human granulosa-lutein cells.

Authors:
Hsun-Ming Chang, M.D., Ph.D., Lanlan Fang, M.D., Ph.D., Jung-Chien Cheng, Ph.D., Elizabeth L. Taylor, M.D., Ying-Pu Sun, M.D., Peter C.K. Leung, Ph.D.

Volume 105, Issue 2, Pages 520-528

Abstract:

Objective:
To investigate the biological role of growth differentiation factor 8 (GDF8) in the regulation of steroidogenesis in human granulosa-lutein (hGL) cells.

Design:
Experimental study.

Setting:
Academic medical center.

Patient(s):
In vitro fertilization patients who provided hGL cells.

Intervention(s):
Cultured hGL cells treated with recombinant human GDF8 for 24 hours.

Main Outcome Measure(s):
Expression of steroidogenic enzymes and steroid production in primary cultures of hGL cells used to investigate the effects of GDF8 via specific mRNA and protein levels examined using real time-quantitative polymerase chain reaction and Western blot analysis, respectively, and levels of estradiol and progesterone measured by enzyme immunoassays.

Result(s):
Extracts were prepared from cultured hGL cells after exposure to GDF8. The levels of cytochrome P450 aromatase (aromatase), the FSH receptor, and estradiol were increased, whereas steroidogenic acute regulatory protein (StAR), luteinizing hormone (LH) receptor, and progesterone levels were decreased after treatment with GDF8. In addition, follicle-stimulating hormone (FSH) stimulated the production of aromatase/estradiol, and LH induced the production of StAR/progesterone. Furthermore, pretreatment with GDF8 for 24 hours enhanced the effects of FSH on aromatase/estradiol induction, whereas GDF8 suppressed the effects of LH on StAR/progesterone stimulation.

Conclusion(s):
In human granulosa cells, GDF8 may play an important role in the modulation of cellular responsiveness to gonadotropins and in the regulation of ovarian steroid production, most likely as a luteinization inhibitor.

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