help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gilling-Smith, C.
Right arrow Articles by Franks, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gilling-Smith, C.
Right arrow Articles by Franks, S.

Journal of Clinical Endocrinology & Metabolism, Vol 79, 1158-1165, Copyright © 1994 by Endocrine Society

ARTICLES

Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries

C Gilling-Smith, DS Willis, RW Beard and S Franks
Department of Obstetrics and Gynecology, St. Mary's Hospital Medical School, Imperial College of Science, Technology, and Medicine, London, United Kingdom.

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.


This article has been cited by other articles:


Home page
 Hum ReprodHome page
R. Homburg
Androgen circle of polycystic ovary syndrome
Hum. Reprod., July 1, 2009; 24(7): 1548 - 1555.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Mortensen, D. A. Ehrmann, E. Littlejohn, and R. L. Rosenfield
Asymptomatic Volunteers with a Polycystic Ovary Are a Functionally Distinct but Heterogeneous Population
J. Clin. Endocrinol. Metab., May 1, 2009; 94(5): 1579 - 1586.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M. Metwally, S. Amer, T.C. Li, and W.L. Ledger
An RCT of metformin versus orlistat for the management of obese anovulatory women
Hum. Reprod., April 1, 2009; 24(4): 966 - 975.
[Abstract] [Full Text] [PDF]

Home page
 Clin Med ResHome page
S. A. R. Doi
Neuroendocrine Dysfunction in PCOS: A Critique of Recent Reviews
Clin. Med. Res., September 1, 2008; 6(2): 47 - 53.
[Full Text] [PDF]

Home page
 ReproductionHome page
A I Qureshi, S S Nussey, G Bano, P Musonda, S A Whitehead, and H D Mason
Testosterone selectively increases primary follicles in ovarian cortex grafted onto embryonic chick membranes: relevance to polycystic ovaries
Reproduction, August 1, 2008; 136(2): 187 - 194.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. Manneras, I. H. Jonsdottir, A. Holmang, M. Lonn, and E. Stener-Victorin
Low-Frequency Electro-Acupuncture and Physical Exercise Improve Metabolic Disturbances and Modulate Gene Expression in Adipose Tissue in Rats with Dihydrotestosterone-Induced Polycystic Ovary Syndrome
Endocrinology, July 1, 2008; 149(7): 3559 - 3568.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
S. Franks, J. Stark, and K. Hardy
Follicle dynamics and anovulation in polycystic ovary syndrome
Hum. Reprod. Update, May 22, 2008; (2008) dmn015v1.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. S. Wachs, M. S. Coffler, P. J. Malcom, S. Shimasaki, and R. J. Chang
Increased Androgen Response to Follicle-Stimulating Hormone Administration in Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1827 - 1833.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
K.A. Walters, C.M. Allan, and D.J. Handelsman
Androgen Actions and the Ovary
Biol Reprod, March 1, 2008; 78(3): 380 - 389.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
V. E. Beshay, J. C. Havelock, R. Sirianni, P. Ye, T. Suzuki, W. E. Rainey, and B. R. Carr
The Mechanism for Protein Kinase C Inhibition of Androgen Production and 17{alpha}-Hydroxylase Expression in a Theca Cell Tumor Model
J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4802 - 4809.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. Manneras, S. Cajander, A. Holmang, Z. Seleskovic, T. Lystig, M. Lonn, and E. Stener-Victorin
A New Rat Model Exhibiting Both Ovarian and Metabolic Characteristics of Polycystic Ovary Syndrome
Endocrinology, August 1, 2007; 148(8): 3781 - 3791.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Mortensen, R. L. Rosenfield, and E. Littlejohn
Functional Significance of Polycystic-Size Ovaries in Healthy Adolescents
J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 3786 - 3790.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
S.K. Blank, C.R. McCartney, and J.C. Marshall
The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome
Hum. Reprod. Update, July 1, 2006; 12(4): 351 - 361.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. C. Marshall
Obesity in Adolescent Girls: Is Excess Androgen the Real Bad Actor?
J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 393 - 395.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
K. Qin, D. A. Ehrmann, N. Cox, S. Refetoff, and R. L. Rosenfield
Identification of a Functional Polymorphism of the Human Type 5 17{beta}-Hydroxysteroid Dehydrogenase Gene Associated with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 270 - 276.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. K. M. Ho, J. R. Wood, D. R. Stewart, K. Ewens, W. Ankener, J. Wickenheisser, V. Nelson-Degrave, Z. Zhang, R. S. Legro, A. Dunaif, et al.
Increased Transcription and Increased Messenger Ribonucleic Acid (mRNA) Stability Contribute to Increased GATA6 mRNA Abundance in Polycystic Ovary Syndrome Theca Cells
J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6596 - 6602.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
E. Diamanti-Kandarakis and C. Piperi
Genetics of polycystic ovary syndrome: searching for the way out of the labyrinth
Hum. Reprod. Update, November 1, 2005; 11(6): 631 - 643.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
S. A.R. Doi, M. Al-Zaid, P. A. Towers, C. J. Scott, and K. A.S. Al-Shoumer
Irregular cycles and steroid hormones in polycystic ovary syndrome
Hum. Reprod., September 1, 2005; 20(9): 2402 - 2408.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
E. J P van Santbrink, F. P Hohmann, M. J C Eijkemans, J. S E Laven, and B. C J M Fauser
Does metformin modify ovarian responsiveness during exogenous FSH ovulation induction in normogonadotrophic anovulation? A placebo-controlled double-blind assessment
Eur. J. Endocrinol., April 1, 2005; 152(4): 611 - 617.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
H. F. Escobar-Morreale, M. Luque-Ramirez, and J. L. San Millan
The Molecular-Genetic Basis of Functional Hyperandrogenism and the Polycystic Ovary Syndrome
Endocr. Rev., April 1, 2005; 26(2): 251 - 282.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
V. L. Nelson-Degrave, J. K. Wickenheisser, K. L. Hendricks, T. Asano, M. Fujishiro, R. S. Legro, S. R. Kimball, J. F. Strauss III, and J. M. McAllister
Alterations in Mitogen-Activated Protein Kinase Kinase and Extracellular Regulated Kinase Signaling in Theca Cells Contribute to Excessive Androgen Production in Polycystic Ovary Syndrome
Mol. Endocrinol., February 1, 2005; 19(2): 379 - 390.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. A. R. Maciel, E. C. Baracat, J. A. Benda, S. M. Markham, K. Hensinger, R. J. Chang, and G. F. Erickson
Stockpiling of Transitional and Classic Primary Follicles in Ovaries of Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5321 - 5327.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. M. Adams, A. E. Taylor, W. F. Crowley Jr., and J. E. Hall
Polycystic Ovarian Morphology with Regular Ovulatory Cycles: Insights into the Pathophysiology of Polycystic Ovarian Syndrome
J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4343 - 4350.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
T. Piltonen, R. Koivunen, A. Perheentupa, L. Morin-Papunen, A. Ruokonen, and J. S. Tapanainen
Ovarian Age-Related Responsiveness to Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3769 - 3775.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
H-W. Yen, A.J. Jakimiuk, I. Munir, and D.A. Magoffin
Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries
Mol. Hum. Reprod., July 1, 2004; 10(7): 473 - 479.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. R. McCartney, A. B. Bellows, M. B. Gingrich, Y. Hu, W. S. Evans, J. C. Marshall, and J. D. Veldhuis
Exaggerated 17-hydroxyprogesterone response to intravenous infusions of recombinant human LH in women with polycystic ovary syndrome
Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E902 - E908.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
W. Zheng, Y.-T. Gao, X.-O. Shu, W. Wen, Q. Cai, Q. Dai, and J. R. Smith
Population-Based Case-Control Study of CYP11A Gene Polymorphism and Breast Cancer Risk
Cancer Epidemiol. Biomarkers Prev., May 1, 2004; 13(5): 709 - 714.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
S. Jonard and D. Dewailly
The follicular excess in polycystic ovaries, due to intra-ovarian hyperandrogenism, may be the main culprit for the follicular arrest
Hum. Reprod. Update, March 1, 2004; 10(2): 107 - 117.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. R. Wood, V. L. Nelson, C. Ho, E. Jansen, C. Y. Wang, M. Urbanek, J. M. McAllister, S. Mosselman, and J. F. Strauss III
The Molecular Phenotype of Polycystic Ovary Syndrome (PCOS) Theca Cells and New Candidate PCOS Genes Defined by Microarray Analysis
J. Biol. Chem., July 11, 2003; 278(29): 26380 - 26390.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Fassnacht, N. Schlenz, S. B. Schneider, S. A. Wudy, B. Allolio, and W. Arlt
Beyond Adrenal and Ovarian Androgen Generation: Increased Peripheral 5{alpha}-Reductase Activity in Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2760 - 2766.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. J. Jakimiuk, S. R. Weitsman, H.-W. Yen, M. Bogusiewicz, and D. A. Magoffin
Estrogen Receptor {alpha} and {beta} Expression in Theca and Granulosa Cells from Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5532 - 5538.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
A. P. Cheung, S. M. Pride, B. H. Yuen, and L. Sy
In-vivo ovarian androgen responses to recombinant FSH with and without recombinant LH in polycystic ovarian syndrome
Hum. Reprod., October 1, 2002; 17(10): 2540 - 2547.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
A. Balen and K. Michelmore
What is polycystic ovary syndrome?: Are national views important?
Hum. Reprod., September 1, 2002; 17(9): 2219 - 2227.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
R. J. Wright, J. M.P. Holly, R. Galea, M. Brincat, and H. D. Mason
Insulin-Like Growth Factor (IGF)-Independent Effects of IGF Binding Protein-4 on Human Granulosa Cell Steroidogenesis
Biol Reprod, September 1, 2002; 67(3): 776 - 781.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. L. Teixeira Filho, E. C. Baracat, T. H. Lee, C. S. Suh, M. Matsui, R. J. Chang, S. Shimasaki, and G. F. Erickson
Aberrant Expression of Growth Differentiation Factor-9 in Oocytes of Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1337 - 1344.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
R. M. Koivunen, L. C. Morin-Papunen, A. Ruokonen, J. S. Tapanainen, and H. K. Martikainen
Ovarian steroidogenic response to human chorionic gonadotrophin in obese women with polycystic ovary syndrome: effect of metformin
Hum. Reprod., December 1, 2001; 16(12): 2546 - 2551.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
S. Greisen, T. Ledet, and P. Ovesen
Effects of androstenedione, insulin and luteinizing hormone on steroidogenesis in human granulosa luteal cells
Hum. Reprod., October 1, 2001; 16(10): 2061 - 2065.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. J. Jakimiuk, S. R. Weitsman, A. Navab, and D. A. Magoffin
Luteinizing Hormone Receptor, Steroidogenesis Acute Regulatory Protein, and Steroidogenic Enzyme Messenger Ribonucleic Acids Are Overexpressed in Thecal and Granulosa Cells from Polycystic Ovaries
J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1318 - 1323.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. N. Vgontzas, R. S. Legro, E. O. Bixler, A. Grayev, A. Kales, and G. P. Chrousos
Polycystic Ovary Syndrome Is Associated with Obstructive Sleep Apnea and Daytime Sleepiness: Role of Insulin Resistance
J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 517 - 520.
[Abstract] [Full Text]

Home page
 Hum ReprodHome page
M.P. Teissier, H. Chable, S. Paulhac, and Y. Aubard
Comparison of follicle steroidogenesis from normal and polycystic ovaries in women undergoing IVF: relationship between steroid concentrations, follicle size, oocyte quality and fecundability
Hum. Reprod., December 1, 2000; 15(12): 2471 - 2477.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
C. Gilling-Smith, H. Mason, D. Willis, S. Franks, and R.W. Beard
In-vitro ovarian steroidogenesis in women with pelvic congestion
Hum. Reprod., December 1, 2000; 15(12): 2570 - 2576.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. Mifsud, S. Ramirez, and E. L. Yong
Androgen Receptor Gene CAG Trinucleotide Repeats in Anovulatory Infertility and Polycystic Ovaries
J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3484 - 3488.
[Abstract] [Full Text]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. K. Wickenheisser, P. G. Quinn, V. L. Nelson, R. S. Legro, J. F. Strauss III, and J. M. McAllister.
Differential Activity of the Cytochrome P450 17{alpha}-Hydroxylase and Steroidogenic Acute Regulatory Protein Gene Promoters in Normal and Polycystic Ovary Syndrome Theca Cells
J. Clin. Endocrinol. Metab., June 1, 2000; 85(6): 2304 - 2311.
[Abstract] [Full Text]

Home page
 Hum ReprodHome page
I.R. Pirwany, R.W.S. Yates, I.T. Cameron, and R. Fleming
Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea
Hum. Reprod., December 1, 1999; 14(12): 2963 - 2968.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
M.P. Teissier, H. Chable, S. Paulhac, and Y. Aubard
Recombinant human follicle stimulating hormone versus human menopausal gonadotrophin induction: effects in mature follicle endocrinology
Hum. Reprod., September 1, 1999; 14(9): 2236 - 2241.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
L. Poretsky, N. A. Cataldo, Z. Rosenwaks, and L. C. Giudice
The Insulin-Related Ovarian Regulatory System in Health and Disease
Endocr. Rev., August 1, 1999; 20(4): 535 - 582.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. F. Strauss III and A. Dunaif
Molecular Mysteries of Polycystic Ovary Syndrome
Mol. Endocrinol., June 1, 1999; 13(6): 800 - 805.
[Full Text]

Home page
 Mol. Endocrinol.Home page
V. L. Nelson, R. S. Legro, J. F. Strauss III, and J. M. McAllister
Augmented Androgen Production Is a Stable Steroidogenic Phenotype of Propagated Theca Cells from Polycystic Ovaries
Mol. Endocrinol., June 1, 1999; 13(6): 946 - 957.
[Abstract] [Full Text]

Home page
 Hum ReprodHome page
M. Fridstrom, K. Carlstrom, P. Sjoblom, and T. Hillensjo
Effect of prednisolone on serum and follicular fluid androgen concentrations in women with polycystic ovary syndrome undergoing in-vitro fertilization
Hum. Reprod., June 1, 1999; 14(6): 1440 - 1444.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
N. Doldi, E. Marsiglio, A. Destefani, A. Gessi, G. Merati, and A. Ferrari
Elevated serum progesterone on the day of HCG administration in IVF is associated with a higher pregnancy rate in polycystic ovary syndrome
Hum. Reprod., March 1, 1999; 14(3): 601 - 605.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
E. Carmina, F. Gonzalez, A. Vidali, F.Z. Stanczyk, M. Ferin, and R.A. Lobo
The contributions of oestrogen and growth factors to increased adrenal androgen secretion in polycystic ovary syndrome
Hum. Reprod., February 1, 1999; 14(2): 307 - 311.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. S. Willis, H. Watson, H. D. Mason, R. Galea, M. Brincat, and S. Franks
Premature Response to Luteinizing Hormone of Granulosa Cells from Anovulatory Women with Polycystic Ovary Syndrome: Relevance to Mechanism of Anovulation
J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3984 - 3991.
[Abstract] [Full Text]

Home page
 NEJMHome page
S. Franks
Polycystic Ovary Syndrome
N. Engl. J. Med., September 28, 1995; 333(13): 853 - 861.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 1994 by The Endocrine Society