Activin & Inhibin

[Bradwaggoner]

http://en.wikipedia.org/wiki/Activin_and_inhibin

Activin

Activin is produced in the gonads, pituitary gland, placenta, and other organs:

In the ovarian follicle, activin increases FSH binding and FSH-induced aromatization. It participates in androgen synthesis enhancing LH action in the ovary and testis. In the male, activin enhances spermatogenesis.

Activin is strongly expressed in wounded skin, and overexpression of activin in epidermis of transgenic mice improves wound healing and enhances scar formation. Its action in wound repair and skin morphogenesis is through stimulation of keratinocytes and stromal cells in a dose-dependent manner.[11]

Activin also regulates the morphogenesis of branching organs such as the prostate, lung, and especially kidney. Activin A increased the expression level of type-I collagen suggesting that activtin A acts as a potent activator of fibroblasts.
Lack of activin during development results in neural development.

Inhibin

In both females and males, inhibin inhibits FSH production and GnRH release from the hypothalamus. However, the overall mechanism differs between the genders:

In females

Inhibin is produced in the gonads, pituitary gland, placenta and other organs.

In women, FSH stimulates the secretion of inhibin from the granulosa cells of the ovarian follicles in the ovaries. In turn, inhibin suppresses FSH.

Inhibin B reaches a peak in the early- to mid-follicular phase, and a second peak at ovulation.

Inhibin A reaches its peak in the mid-luteal phase.

Inhibin secretion is diminished by GnRH, and enhanced by insulin-like growth factor-1 (IGF-1).

In males
In men, it is a hormone that inhibits FSH by negative feedback. It is secreted from the Sertoli cells,[12] located in the seminiferous tubules inside the testes. Androgens stimulate inhibin production; this peptide may also help to locally regulate spermatogenesis.

[Bradwaggoner]

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T3G-3XVH3M8-2W&_user=10&_coverDate=01%2F31%2F1995&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1519255380&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=170441111bd90d59f1e6540bac8a0824&searchtype=a

Activin and inhibin have opposite effects on steroid 5α-reductase activity in genital skin fibroblasts

I. Antonipillai, M. Wahe, J. Yamamoto and R. Horton
University of Southern California, Division of Endocrinology, Los Angeles, CA 90033, USA
Received 22 August 1994; accepted 31 October 1994. ; Available online 10 November 1999.
Abstract

The transforming growth factor β (TGF-β) superfamily includes several closely related peptides including the activins and inhibins. Since we recently reported that TGF-β1 and β2 are potent inducers of steroid 5α-reductase (5αR), we have now studied the effects of these other peptides using primary cultures of human scrotal skin fibroblasts. Recombinant human activin A or inhibin A were added to cultured cells (2 × 105 cells) for 2 days in a serum free media and 5αR activity was measured by the %-conversion of tracer [3H]-testosterone to dihydrotestosterone (DHT) over a 4-h period. Activin significantly stimulated 5αR activity in a dose related manner (control 3.0 ± 0.4%, activin (1.2 × 10−9 M) 6 ± 0.7%, P < 0.01, (2.4 × 10−9 M) 8.5 ± 0.6%, P < 0.001). In comparison, androgen (DHT 10−7 M) induction of 5αR was 4.7 ± 0.2%, P < 0.05. Combined exposure of fibroblasts to activin (1.2 × 10−9 M) and androgen (10−7 M) did not result in additive or synergistic effect on 5αR activity. In contrast, exposure of cells to an androgen (10−7 M) and TGF-β (2 × 10−10 M) led to synergistic effects on 5αR activity (control 1.5 ± 0.1%, DHT 2.6 ± 0.2% TGF-β1 4.8 ± 0.5, TGF-β1+DHT 9.2 ± 1.2%). Finasteride, a 4-aza steroid inhibitor of 5αR (10−8 M) inhibited both activin and TGF-β-induced 5αR activity suggesting that the type II isoenzyme is induced by these peptides. Activin mediated 5αR activity was abolished by the addition of cycloheximide, consistent with the proposition that enzyme induction requires new protein synthesis. Recombinant human inhibin alone did not alter basal 5αR activity but dose dependently inhibited DHT (10−7 M)-induced 5αR activity (control 4.1 ± 0.4%, DHT 7.5 ± 0.7%, DHT + inhibin (0.6 × 10−9 M) 5.7 ± 0.5%, P < 0.05 DHT + inhibin (1.2 × 10−9 M] 4.3 ± 0.2%, P < 0.001). The effects of activin or inhibin were not associated with changes in cell number or thymidine uptake. These studies indicate that activin is 100 times more potent on a molar basis than androgen in induction of 5αR activity. Although both activin and TGF-β1 induce 5αR activity, the actions of the two peptides differ in the presence of an androgen. In contrast, inhibin significantly inhibits androgen induction of 5αR. Activin and inhibin, two closely related molecules, potentially play opposite roles in DHT formation in sexual tissue.

[Bradwaggoner]

http://www.rndsystems.com/cb_detail_objectname_FA01_BMPs.aspx

BMPs Influence FSH Synthesis

Follicle-stimulating hormone (FSH) is produced as an alpha/beta heterodimer within pituitary gonadotropes. Synthesis of the beta-subunit of FSH is the rate-limiting step in its overall production. Members of the TGF-beta superfamily have been shown to regulate the synthesis of FSH beta. Activin, for example, stimulates secretion of FSH by increasing FSH beta gene expression at the transcriptional level.1,2 Inhibin, although structurally similar to activin, is a negative regulator of FSH beta gene expression.3 Additional evidence that supports the influence of activin and inhibin on FSH synthesis has been generated with knockout mice. Mice lacking the Activin ActRII receptors have significantly reduced serum FSH levels, thus emphasizing the importance of activin in inducing FSH expression.4 Activin /Inhibin betaB knockout mice, by contrast, demonstrate slightly elevated levels of serum FSH.4 Bone morphogenetic protein (BMP)-7, another TGF-beta superfamily member, can bind ActRII and transduce an activin-like signal, suggesting the possibility that it may serve as an alternative ligand for induction of FSH beta in the absence of activin. 5 Levels of BMP-7 were not measured, however, in the knockout mice studies previously listed.

In a recent study by Huang et al.,6 a functional BMP system is identified within gonadotropes demonstrating that BMPs play a novel role in regulating FSH synthesis in the pituitary. Transient expression of oFSH beta Luc (ovine FSH beta promoter linked to a luciferase reporter gene) in a transformed gonadotrope cell line, LbetaT2, is induced 4-fold by BMP-7 or BMP-6 treatment. BMP-7 and BMP-6 also increase endogenous FSH secretion by 10- and 14-fold, respectively, from LbetaT2 cells, demonstrating for the first time that BMP-7 and BMP-6 may be significant FSH stimulators. BMP-7 or BMP-6 can also stimulate oFSH beta Luc expression in primary pituitary cell cultures derived from transgenic mice. Neutralizing antibodies to BMP-7, which do cross-react with BMP-6 but not Activin A, decrease basal oFSH beta Luc expression and FSH secretion from the transgenic mouse pituitary cultures. Neutralizing antibodies to either Activin A or Activin B, however, do not significantly decrease basal oFSH beta Luc expression and FSH secretion. Detection of BMP-7 and BMP-6 mRNA in the transgenic mouse pituitary cells confirmed that BMP-7 and BMP-6 were being produced by these cells. Collectively, these results suggest an autocrine or paracrine role for the TGF-beta superfamily members, BMP-7 and BMP-6, in promoting FSH synthesis.