Review Article

The Role of Androgen Hormones in Early Follicular Development

Table 4

Effects of the in vitro administration of androgen hormones on early follicular development.

AnimalMethodology usedMain resultsReference

CattleCulture of ovarian cortex fragments for 10 days in the presence of (i) 10−10 to 10−7 M testosterone, (ii) 10−7 M estradiol, and (iii) testosterone in combination with flutamide (AR antagonist). Testosterone (10−7 and 10−6 M) promoted an increased transition from primary to secondary follicles, which was inhibited in the presence of flutamide and was not replicated in the presence of estradiol. Yang and Fortune, 2006 [85]

HumanCulture of ovarian cortex fragments for 24 hours in the presence of FSH in combination with (i) 10−10 to 10−7 M testosterone, (ii) 10−10 to 10−7 M dihydrotestosterone, (iii) 10−10 to 10−8 M estradiol, and (iiii) dihydrotestosterone in combination with casodex (AR antagonist).Androgens promoted a reduction of ovarian tissue apoptosis which was inhibited in the presence of casodex and was not replicated in the presence of estradiol.Otala et al., 2004 [87]

RodentCulture of isolated preantral follicles for 6 days in the presence of (i) anti-androgen antibody in combination or not with 1  g/mL androstenedione, (ii) casodex (AR antagonist) in combination with FSH, and (iii) 1  g/mL dihydroxytestosterone in combination with FSH. Treatment with an anti-androgen antibody inhibited follicular growth and differentiation; an effect that was reversed by the addition of androstenedione. Treatment with casodex inhibited the positive effect of FSH on follicular growth which was reversed by the addition of dihydroxytestosterone.Murray et al., 1998 [21]
Culture of isolated preantral follicles for 6 days in the presence of FSH in combination or not with 1  g/mL androstenedione. Treatment with FSH promoted follicular growth and differentiation which were improved when FSH was combined with androstenedione.Spears et al., 1998 [89]
Culture of isolated preantral follicles for 4 days in the presence of (i) dihydrotestosterone or testosterone or dihydroxytestosterone or dihydroxytestosterone sulfate (10−11 to 10−7 M) (ii) in combination or not with hydroxyflutamide (AR antagonist) or FSH. Treatment with the different androgens promoted a dose-dependent follicular growth which was inhibited by the presence of the AR antagonist. The combination with FSH improved the effect of androgens on follicular growth. Wang et al., 2001 [22]
Culture of isolated preantral follicles for 13 days in the presence of (i) 50  M hydroxyflutamide (AR antagonist) in combination with FSH and (ii) 50  M bicalutamide (AR antagonist) in combination with FSH. Follicular growth, production of inhibiting B, and steroids and oocyte maturation were impaired by the addition of both AR antagonists. Lenie and Smitz 2009 [20]
Culture of isolated preantral follicles for 13 days in the presence of (i) 20 or 200 nM androstenedione and (ii) testosterone (20 or 200 nM or 2  M) both in the presence of FSH. Treatment with both androgens at concentrations of more than 200 nM impaired oocyte maturation.Romero and Smitz, 2010 [92]
Culture of isolated preantral follicles for 10 days in the presence of 10−5 M androstenedione. Treatment with androstenedione induced changes in the morphology of granulosa cells compatible with luteinization.Okutsu et al., 2010 [90]
Culture of isolated preantral follicles for 12 days in the presence of androstenedione (10−11, 10−9, 10−5 M) in combination with FSH.Treatment with androstenedione at the dose of 10−5 M promoted follicular growth, whereas higher doses impaired follicular development. Treatment with androstenedione impaired oocyte maturation regardless of the dose used.Tarumi et al., 2012 [91]