Cited by 301Ovarian function and disordersReproductive Biology and FertilityAdrenal Hormones and Disorders

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Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome

Gilling‐Smith, C., Story, H, Rogers, V., Franks, S.·1997·Clinical Endocrinology

DOI 10.1046/j.1365-2265.1997.2321049.x

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Abstract

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrinopathy of unknown aetiology. The aims of this study were to identify whether ovarian thecal cell steroidogenesis is abnormally regulated in PCOS by measuring steroid responses to a single dose of hCG before, and during, suppression of endogenous LH levels by GnRH analogue (GnRHa). DESIGN: Serum levels of LH, FSH, 17 alpha hydroxyprogesterone (17OHP), androstenedione, testosterone and dehydroepiandrosterone sulphate were measured before, and 48 hours after, a single intramuscular injection of 10,000 IU hCG. The test was repeated 4 weeks after suppression of endogenous LH levels by GnRHa. PATIENTS: The ovarian responses to hCG were compared in three groups of women. Eleven women had normal ovaries and regular cycles, eight had polycystic ovaries but not clinical features of the syndrome (PCO group) and eight had polycystic ovaries, anovulation and either severe hirsutism or alopecia (PCOS group). RESULTS: Before GnRHa treatment, LH levels were significantly higher in the PCOS group but hCG stimulated a similar rise in 17OHP in all three groups. Following analogue, LH levels were suppressed in all three groups but the 17OHP responses to hCG were significantly higher in both the PCO and PCOS groups compared with normal controls. CONCLUSIONS: These findings provide further evidence in favour of an intrinsic abnormality of thecal cell steroidogenesis in the polycystic ovary.

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Tosi, F., Negri, C., Perrone, F., Dorizzi, R. M., Castello, R., Bonora, E., & Moghetti, P. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-2939 · Cited by 90
The Rationale for Banning Human Chorionic Gonadotropin and Estrogen Blockers in Sport
Handelsman, D. J. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-2569 · Cited by 91
“The minority of women with PCOS with higher baseline blood testosterone concentrations have slightly higher increases (2–3 nmol/liter) (74, 75, 81), but these remain of small magnitude in quantitative terms for myotrophic effects.”
Background
PCOS in adolescents
Diamanti‐Kandarakis, E. (2009) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2009.09.005 · Cited by 92
Comparison of Simvastatin and Metformin in Treatment of Polycystic Ovary Syndrome: Prospective Randomized Trial
Banaszewska, B., Pawelczyk, L. A., Spaczyński, R., & Dulęba, A. J. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1674 · Cited by 89
Endocrine Disrupting Chemicals in Polycystic Ovary Syndrome: The Relevant Role of the Theca and Granulosa Cells in the Pathogenesis of the Ovarian Dysfunction
Józkowiak, M., Piotrowska‐Kempisty, H., Kobylarek, D., Gorska, N., Mozdziak, P. E., Kempisty, B., Rachoń, D., & Spaczyński, R. (2022) · Cells · doi:10.3390/cells12010174 · Cited by 96
Ovarian Morphology Is a Marker of Heritable Biochemical Traits in Sisters with Polycystic Ovaries
Franks, S., Webber, L. J., Goh, M. J., Valentine, A., White, D. M., Conway, G. S., Wiltshire, S., & McCarthy, M. I. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0369 · Cited by 88
Self-citation
Adiponectin and Its Receptors in the Ovary: Further Evidence for a Link between Obesity and Hyperandrogenism in Polycystic Ovary Syndrome
Comim, F. V., Hardy, K., & Franks, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0080416 · Cited by 89
“Hyperandrogenism is the hallmark of PCOS and originates predominantly from ovarian thecainterstitial cells, which are characterised by an increased capacity for androgen biosynthesis [3-6].”
BackgroundSelf-citation
The physiological basis of complementary and alternative medicines for polycystic ovary syndrome
Raja-Khan, N. T., Stener‐Victorin, E., Wu, X., & Legro, R. S. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00667.2010 · Cited by 88
“Ovarian hyperandrogenemia, the most consistent endocrine feature, probably plays a key role (30), but hyperinsulinemia/insulin resistance and abdominal obesity are also thought to be important (4).”
Background
Retinoids and Retinol Differentially Regulate Steroid Biosynthesis in Ovarian Theca Cells Isolated from Normal Cycling Women and Women with Polycystic Ovary Syndrome
Wickenheisser, J. K., Nelson-DeGrave, V. L., Hendricks, K. L., Legro, R. S., Strauss, J. F., & McAllister, J. M. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0330 · Cited by 82
POLYCYSTIC OVARY SYNDROME
Taylor, A. E. (1998) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/s0889-8529(05)70045-1 · Cited by 80
Effects of Curcumin on Glycemic Control and Lipid Profile in Polycystic Ovary Syndrome: Systematic Review with Meta-Analysis and Trial Sequential Analysis
Chien, Y.-J., Chang, C., Wu, M., Chen, C., Horng, Y.-S., & Wu, H.-C. (2021) · Nutrients · doi:10.3390/nu13020684 · Cited by 82
“The pathophysiology of PCOS is complex and is believed to involve functional ovarian hyperandrogenism caused by hyperresponsiveness to the stimulation of luteinizing hormone and failed downregulation of thecal androgen production [8,9].”
Background
Environmental Control of Biological Rhythms: Effects on Development, Fertility and Metabolism
Amaral, F. G., Castrucci, A. M., Cipolla‐Neto, J., Poletini, M. O., Mendez, N., Richter, H. G., & Sellix, M. T. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12144 · Cited by 80
The Polycystic Ovary Morphology-Polycystic Ovary Syndrome Spectrum
Rosenfield, R. L. (2014) · Journal of Pediatric and Adolescent Gynecology · doi:10.1016/j.jpag.2014.07.016 · Cited by 76
“This includes some asymptomatic young 258 women who meet criteria for ovulatory PCOS.”
Influential
Variation within the Type 2 Diabetes Susceptibility Gene Calpain-10 and Polycystic Ovary Syndrome
Haddad, L., Evans, J. C., Gharani, N., et al. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.6.8608 · Cited by 76
“SHBG was measured using the Immulite method (Diagnostic Products, Llanberis, UK) (1, 30).”
MethodSelf-citation
A review of the hormones involved in the endocrine dysfunctions of polycystic ovary syndrome and their interactions
Emanuel, R. H. K., Roberts, J., Docherty, P. D., Lunt, H., Campbell, R. E., & Möller, K. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1017468 · Cited by 87
Insulin modulation of luteinizing hormone secretion in normal female volunteers and lean polycystic ovary syndrome patients
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“PCOS women have an abnormal ovarian steroid response to gonadotropin stimulation [”
Background
State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)
Geller, D. H., Pacaud, D., Gordon, C. M., & Misra, M. (2011) · International Journal of Pediatric Endocrinology · doi:10.1186/1687-9856-2011-9 · Cited by 72
“A genetic etiology for PCOS has been established on the basis of familial clustering [6,21,43-45], with heritability estimates as high as 0.”
Background
Asymptomatic Volunteers with a Polycystic Ovary Are a Functionally Distinct but Heterogeneous Population
Mortensen, M., Ehrmann, D. A., Littlejohn, E., & Rosenfield, R. L. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2771 · Cited by 69
Implicating androgen excess in propagating metabolic disease in polycystic ovary syndrome
Kempegowda, P., Melson, E., Manolopoulos, K. N., Arlt, W., & O’Reilly, M. (2020) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018820934319 · Cited by 78
Reappraising the relationship between hyperinsulinemia and insulin resistance in PCOS
Houston, E. J., & Templeman, N. M. (2025) · Journal of Endocrinology · doi:10.1530/joe-24-0269 · Cited by 93
Polycystic ovary syndrome: etiology and pathogenesis
Matalliotakis, I., Kourtis, A., Koukoura, O., & Panidis, D. (2006) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-006-0171-x · Cited by 68
“Furthermore, patients with PCOS continue to exhibit 17-hydroxyprogesterone hyperresponsiveness to hCG despite correction of their baseline LH abnormality by 1 month of GnRH agonist treatment [ 59 ].”
Background
Introducing a rat model of prenatal androgen‐induced polycystic ovary syndrome in adulthood
Tehrani, F. R., Noroozzadeh, M., Zahediasl, S., Piryaei, A., & Azizi, F. (2014) · Experimental Physiology · doi:10.1113/expphysiol.2014.078055 · Cited by 68
“Experimental Physiology C© 2014 The Physiological Society female offspring.”
BackgroundInfluential
The diagnosis of polycystic ovary syndrome: the criteria are insufficiently robust for clinical research
Barth, J. H., Yasmin, E., & Balen, A. H. (2007) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2007.02932.x · Cited by 66
Association of Insulin Gene VNTR Polymorphism with Polycystic Ovary Syndrome
Vaňková, M., Vrbíková, J., Hill, M., Cinek, O., & Bendlová, B. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb04317.x · Cited by 65
Valproate Inhibits the Conversion of Testosterone to Estradiol and Acts as an Apoptotic Agent in Growing Porcine Ovarian Follicular Cells
Taubøll, E., Gregoraszczuk, E. Ł., Kołodziej, A., Kajta, M., & Ropstad, E. (2003) · Epilepsia · doi:10.1046/j.1528-1157.2003.60702.x · Cited by 64
Increased Cytochrome P450 17α-Hydroxylase Promoter Function in Theca Cells Isolated from Patients with Polycystic Ovary Syndrome Involves Nuclear Factor-1
Wickenheisser, J. K., Nelson-DeGrave, V. L., Quinn, P. G., & McAllister, J. M. (2003) · Molecular Endocrinology · doi:10.1210/me.2003-0090 · Cited by 63
The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis
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“An intrinsic abnormality in the steroidogenic machinery of the ovarian theca cells is suggested to be one reason for increased androgen biosynthesis frequently associated with PCOS [94,95].”
Background
Testosterone a key factor in gender related metabolic syndrome
Bianchi, V. E., & Locatelli, V. (2018) · Obesity Reviews · doi:10.1111/obr.12633 · Cited by 65
“Ovaries have a great sensibility to insulin, and the chronic stimulation of ovaries by insulin determines a hypersecretion of androgens (160).”
Background
Adiponectin: A New Regulator of Female Reproductive System
Dobrzyń, K., Smolińska, N., Kieżun, M., Szeszko, K., Rytelewska, E., Kisielewska, K., Gudelska, M., & Kamiński, T. (2018) · International Journal of Endocrinology · doi:10.1155/2018/7965071 · Cited by 60
“Theca cells are recognized as one of the primary sources of excess androgen biosynthesis in women with PCOS [75].”
BackgroundInfluential
High-fat high-sugar diet induces polycystic ovary syndrome in a rodent model†
Roberts, J. S., Perets, R. A., Sarfert, K. S., Bowman, J. J., Ozark, P. A., Whitworth, G. B., Blythe, S. N., & Toporikova, N. (2017) · Biology of Reproduction · doi:10.1095/biolreprod.116.142786 · Cited by 58
Weight management interventions in women with and without PCOS: a systematic review
Kataoka, J., Tassone, E., Misso, M., Joham, A., Stener-Victorin, E., Teede, H., & Moran, L. (2017) · Nutrients · doi:10.3390/nu9090996 · Cited by 58

Authors: Gilling‐Smith, C., Story, H., Rogers, V., & Franks, S.
Affiliations: St Mary's Hospital (GB)
Corresponding author: Gilling‐Smith, C.
ORCID: Franks, S.
Venue: Clinical Endocrinology
Publisher: Wiley
Published: 1997-07
Volume: 47
Issue: 1
Pages: 93-99
ISSN: 0300-0664 (ISSN-L)
1365-2265
DOI: 10.1046/j.1365-2265.1997.2321049.x
OpenAlex: W2141227160
Cited by: 301
References: 0
Citations by year: 2026: 3 · 2025: 11 · 2024: 11 · 2023: 5 · 2022: 15 · 2021: 10 · 2020: 8 · 2019: 12 · 2018: 8 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 13 · 2013: 16 · 2012: 16
FWCI: 8.74
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2311 d)
Locations: Clinical Endocrinology (publishedVersion)
PubMed (publishedVersion)
Funders: Bayer Corporation
Topics: Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: polycystic ovary syndrome, hCG stimulation test, 17-hydroxyprogesterone, GnRH analogues, LH suppression, androstenedione, testosterone, dehydroepiandrosterone sulfate, hirsutism, anovulation
MeSH terms: Adolescent, Adult, Androstenedione, Female, Chorionic Gonadotropin, Gonadotropins, Pituitary, Humans, Luteinizing Hormone, Gonadotropin-Releasing Hormone, Middle Aged, Polycystic Ovary Syndrome, Gonadal Steroid Hormones, Testosterone, Theca Cells, Dehydroepiandrosterone Sulfate, 17-alpha-Hydroxyprogesterone

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Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome

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