It has been suggested that measurements of serum 3 Alpha-androstanediol (3 Alpha-diol) reflect peripheral androgen production (PAP). Recently, we have shown that serum 3 Alpha-diol glucuronide (3 ALpha-diol G) is derived almost exclusively from extrasplanchnic sources and is a better marker of PAP than is unconjugated 3 Alpha-diol. In women with idiopathic hirsutism, we found that virtually all women had elevated levels of 3 Alpha-diol G despite normal levels of other androgens. In patients with polycystic ovary syndrome (PCO), we have shown that while all women exhibit elevated levels of androgens derived from glandular sources, the presence or absence of hirsutism may be explained by PAP as reflected by measurements of serum 3 Alpha-diol G. Nevertheless, the blood source of 3 Alpha-diol G has not been established. It is not known whether blood levels of DHT and 3 Alpha-diol G are in equilibrium or if they exist in separate pools. 3 Alpha-diol G is produced, in part, via 5 Alpha reductase (5 Alpha R) and probably reflect 5 Alpha R activity in peripheral tissues. Therefore, we will attempt to correlate serum 3 Alpha-diol G with in vitro 5 Alpha R activity in women. Spironolactone (S) is a receptor blocking agent which improves hirsutism in PCO. Whether S therapy changes serum 3 Alpha-diol G and if this correlates with the improvement in hirsutism should be investigated. In project #1 we propose to obtain blood and genital skin from 15 ovulatory premenopausal patients, from 15 hirsute (H) women with PCO and from 15 normal men. We will attempt to correlate measurements of serum DHT, 3 Alpha-diol G with in vitro DHT and 3 Alpha-diol production. In project #2, 3H-DHEA, 3H-Adione and 3H-DHT will be infused intravenously into 10 H-PCO women and 6 controls until steady state occurs. Conversion ratios between these precursor steroids and 3 alpha-diol G will be calculated. In addition, a 2-day dexamethasone suppression test and a 6-hour ACTH infusion will be carried out in order to help determine the source of serum 3 Alpha-diol G. In project #3, 30 H-PCO women will be treated with S and have the clinical assessment of hirsutism and hormonal measurements carried out before and after treatment at 3-month intervals for 18 months. Hair shaft diameters will be recorded and genital skin biopsies will be obtained after treatment in 10 patients. These studies will help establish the prevalence of PAP and increased 5 Alpha R activity in PCO, the clinical usefulness of measurements of 3 Alpha-diol G and its source(s) in blood. The clinical benefits of treatment with S in H-PCO women will be compared with the assessment of any changes in PAP as reflected by measuremets of 3 Alpha-diol and in 5 Alpha R activity.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Unknown (R23)
Project #
Application #
Study Section
Reproductive Biology Study Section (REB)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Schools of Medicine
Los Angeles
United States
Zip Code
Anderson, R E; Ben-Rafael, Z; Flickinger, G L et al. (1988) Secretory dynamics of bioactive and immunoreactive prolactin in polycystic ovary syndrome. Fertil Steril 49:239-43
Vermesh, M; Silva, P D; Rosen, G F et al. (1988) Effect of androgen on adrenal steroidogenesis in normal women. J Clin Endocrinol Metab 66:128-30
Barnes, R B; Artal, R; Lobo, R A (1987) Peripheral dopamine metabolism in polycystic ovary syndrome. Obstet Gynecol 70:153-6
Serafini, P; Paulson, R J; Francis, M M et al. (1987) Modulation of prolactin responses to gonadotropin releasing hormone by acute testosterone infusions in normal women. Gynecol Endocrinol 1:247-53
Lobo, R A; Paul, W L; Gentzschein, E et al. (1987) Production of 3 alpha-androstanediol glucuronide in human genital skin. J Clin Endocrinol Metab 65:711-4
Silva, P D; Gentzschein, E E; Lobo, R A (1987) Androstenedione may be a more important precursor of tissue dihydrotestosterone than testosterone in women. Fertil Steril 48:419-22
Rosen, G F; Lobo, R A (1987) Further evidence against dopamine deficiency as the cause of inappropriate gonadotropin secretion in patients with polycystic ovary syndrome. J Clin Endocrinol Metab 65:891-5
Paulson, R J; Bernstein, G S; Marrs, R P et al. (1986) Idiopathic oligospermia and peripheral androgen metabolism. Fertil Steril 46:480-3
Serafini, P; Silva, P D; Paulson, R J et al. (1986) Acute modulation of the hypothalamic-pituitary axis by intravenous testosterone in normal women. Am J Obstet Gynecol 155:1288-92
Barnes, R B; Cha, K Y; Lee, D G et al. (1986) Modulation of luteinizing hormone immunoreactivity and bioactivity by dopamine but not norepinephrine in women. Am J Obstet Gynecol 154:445-50

Showing the most recent 10 out of 23 publications