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Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries.
J Clin Endocrinol Metab. 1994 Oct; 79(4):1158-65.JC

Abstract

The aim of this study was to examine the hypothesis that hypersecretion of ovarian androgens in polycystic ovary syndrome results from an intrinsic abnormality of androgen biosynthesis by thecal cells. Steroid accumulation by human thecal cells from normal and polycystic ovaries (PCO-theca) was examined under basal and LH-stimulated conditions. A method for dispersing and culturing human thecal cells as primary monolayers in serum-free medium was developed. LH increased androstenedione (A), progesterone (P), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, and estradiol accumulation in the overlying medium in a dose-dependent manner at a maximum effective dose of 2.5 ng/mL. The principal variables affecting the magnitude of steroid accumulation were plating density, duration of incubation, and follicle size. Using only theca from follicles less than 10 mm and keeping plating density constant, 48-h steroid production by theca from five normal ovaries was compared to that from nine polycystic ovaries isolated from both anovulatory and ovulatory women. There was a significant increase in both basal (median, 32.1 pmol/1000 cells.48 h; range, 18.7-250) and LH-stimulated (56 pmol/1000 cells; range, 40.7-406) A accumulation by PCO-theca compared to basal (1.7 pmol/1000 cells; range, 1.1-4.3) and LH-stimulated (2.8 pmol/1000 cells; range, 2.0-8.1) A accumulation by normal theca, with no overlap in values between the two. Although P production was also increased in the PCO-theca, the A to P ratios under both basal and LH-stimulated conditions were significantly higher in the PCO-theca [A/P ratio normal; PCO basal, 0.1 and 0.53 (P < 0.01); LH-stimulated, 0.04 and 0.65 (P < 0.001)], suggesting increased conversion of P to A. The steroid response to LH was similar in both groups. This is the first report of a difference in thecal androgen production between normal and polycystic ovaries and supports the hypothesis that there is a primary abnormality in the regulation of androgen production in PCOS.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, St. Mary's Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7962289

Citation

Gilling-Smith, C, et al. "Hypersecretion of Androstenedione By Isolated Thecal Cells From Polycystic Ovaries." The Journal of Clinical Endocrinology and Metabolism, vol. 79, no. 4, 1994, pp. 1158-65.
Gilling-Smith C, Willis DS, Beard RW, et al. Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. J Clin Endocrinol Metab. 1994;79(4):1158-65.
Gilling-Smith, C., Willis, D. S., Beard, R. W., & Franks, S. (1994). Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. The Journal of Clinical Endocrinology and Metabolism, 79(4), 1158-65.
Gilling-Smith C, et al. Hypersecretion of Androstenedione By Isolated Thecal Cells From Polycystic Ovaries. J Clin Endocrinol Metab. 1994;79(4):1158-65. PubMed PMID: 7962289.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. AU - Gilling-Smith,C, AU - Willis,D S, AU - Beard,R W, AU - Franks,S, PY - 1994/10/1/pubmed PY - 1994/10/1/medline PY - 1994/10/1/entrez SP - 1158 EP - 65 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 79 IS - 4 N2 - The aim of this study was to examine the hypothesis that hypersecretion of ovarian androgens in polycystic ovary syndrome results from an intrinsic abnormality of androgen biosynthesis by thecal cells. Steroid accumulation by human thecal cells from normal and polycystic ovaries (PCO-theca) was examined under basal and LH-stimulated conditions. A method for dispersing and culturing human thecal cells as primary monolayers in serum-free medium was developed. LH increased androstenedione (A), progesterone (P), 17 alpha-hydroxyprogesterone, dehydroepiandrosterone, and estradiol accumulation in the overlying medium in a dose-dependent manner at a maximum effective dose of 2.5 ng/mL. The principal variables affecting the magnitude of steroid accumulation were plating density, duration of incubation, and follicle size. Using only theca from follicles less than 10 mm and keeping plating density constant, 48-h steroid production by theca from five normal ovaries was compared to that from nine polycystic ovaries isolated from both anovulatory and ovulatory women. There was a significant increase in both basal (median, 32.1 pmol/1000 cells.48 h; range, 18.7-250) and LH-stimulated (56 pmol/1000 cells; range, 40.7-406) A accumulation by PCO-theca compared to basal (1.7 pmol/1000 cells; range, 1.1-4.3) and LH-stimulated (2.8 pmol/1000 cells; range, 2.0-8.1) A accumulation by normal theca, with no overlap in values between the two. Although P production was also increased in the PCO-theca, the A to P ratios under both basal and LH-stimulated conditions were significantly higher in the PCO-theca [A/P ratio normal; PCO basal, 0.1 and 0.53 (P < 0.01); LH-stimulated, 0.04 and 0.65 (P < 0.001)], suggesting increased conversion of P to A. The steroid response to LH was similar in both groups. This is the first report of a difference in thecal androgen production between normal and polycystic ovaries and supports the hypothesis that there is a primary abnormality in the regulation of androgen production in PCOS. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/7962289/Hypersecretion_of_androstenedione_by_isolated_thecal_cells_from_polycystic_ovaries_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.79.4.7962289 DB - PRIME DP - Unbound Medicine ER -