Activin B is produced early in antral follicular development and suppresses thecal androgen production

Abstract

Little is known about the role of activin B during folliculogenesis. This study investigated the expression levels of activin/inhibin subunits (βA, βB, and α), steroid enzyme, and gonadotrophin receptors in theca (TC) and granulosa cells (GC) by QPCR and activin A and B and inhibin A protein levels in follicular fluid (FF) of developing sheep follicles during estrus and anestrus. The effect of activin B on androgen production from primary TC cultures in vitro was also assessed. During folliculogenesis, in anestrus and estrus, FF activin B concentrations and thecal and GC activin βB mRNA levels decreased as follicle diameter increased from 1–3 to >6 mm regardless of estrogenic status. Estrogenic preovulatory follicles had reduced concentrations of FF activins B and A, and TC and GCs expressed higher levels of activin βA mRNA at 3–4 mm, and TCs more inhibin α mRNA at >4 mm stages of development compared with nonestrogenic follicles. Activin B decreased androstenedione production from primary TCs in vitro, an effect blocked by inhibin A. Thus, sheep follicles 1–3 mm in diameter contained high FF levels of activin B, which decreased as the follicle size increased, and, like activin A, suppressed thecal androgen production in vitro, an effect blocked by inhibin. Furthermore, the theca of large estrogenic follicles expressed high levels of inhibin α and activin βA mRNA suggesting local thecal derived inhibin A production. This would inhibit the negative effects of thecal activins B and A ensuring maximum androgen production for enhanced estradiol production by the preovulatory follicle(s).

Activin A and follistatin during the oestrous cycle and early pregnancy in ewes

“…The preovulatory follicle strongly expresses INHBA mRNA (Engelhardt et al 1993, Tisdall et al 1994, and this peak could be driven by growth of the preovulatory follicle. However, concentrations of activin A were not higher in follicular fluid of oestrogen-active follicles than oestrogeninactive follicles (Young et al 2012); so, the source of the peak of activin A observed around oestrous needs to be confirmed.…”

Activin A, B and AB decrease progesterone production by down-regulating StAR in human granulosa cells

“…In the follicular fluid, the expression of differential activin isoforms is exhibited in a species-specific manner. Specifically, follicular fluid activin A and activin B concentrations decrease as antral follicle size increases in sheep (Young et al, 2012). In humans and pigs, follicular fluid activin A and activin AB concentrations are similar (Evans et al, 1997).…”

“…Human ovarian follicles express both inhibin βA and inhibin βB subunits that lead to the production of three activin isoforms, activin A (βA and βA), activin B (βB and βB) and activin AB (βA and βB) (Evans et al, 1997;Sidis et al, 1998;Young et al, 2012). Antral follicular fluid was found to contain activins A, B and AB in many mammal species, including humans (Evans et al, 1997;Young et al, 2012).…”

“…Human ovarian follicles express both inhibin βA and inhibin βB subunits that lead to the production of three activin isoforms, activin A (βA and βA), activin B (βB and βB) and activin AB (βA and βB) (Evans et al, 1997;Sidis et al, 1998;Young et al, 2012). Antral follicular fluid was found to contain activins A, B and AB in many mammal species, including humans (Evans et al, 1997;Young et al, 2012). The expression of activins and their type I and type II receptors in ovarian follicles from the early follicular phase indicates that activins may act through autocrine or paracrine mechanisms to regulate follicle progression (Drummond et al, 2002;Rabinovici et al, 1991).…”

Activin B Promotes Initiation and Development of Hair Follicles in Mice

“…However, in this study, we found no significant difference between male and female mice in either of the groups. Two reasons could be provided: one may be the younger age of mice (7 or even 6 weeks old) with a relatively low level of hormones; the other reason is that activin B not only decreases androstenedione production from primary theca cells but also regulates the synthesis of estrogen [Bernard et al, 2006;Young et al, 2012]. This result may be due to the interaction among them; the relative mechanism in this progress has not yet been determined.…”