Transforming Growth Factor ß1: An Autocrine Regulator of Adrenocortical Steroidogenesis

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Abstract
Transforming growth factor ß1 (TGFß1) is a member of a large family of structurally related regulatory polypeptides which comprises both functionally similar (TGFß1, TGFß2, TGFß3, TGFß4 and TGFß5) and functionally distinct proteins. In the past few years, TGFß1 has emerged as a multifunctional protein. One of its remarkable properties is its capacity to negatively modulate the differentiated, steroïdogenic adrenocortical functions. We present here a review of the results from our recent work related to the effects of TGFß1 on bovine adrenocortical cell (zona fasciculata-reticularis) functions. We identified the steroid 17α-hydroxylase (P-45017α) biosynthetic enzyme and the angiotensin II receptor as major targets whose expression are negatively regulated by TGFß1 in these cells. We characterized TGFß1 receptors at the surface of adrenocortical cells (mainly type I and type III receptors) and observed that their number is increased under ACTH treatment. Furthermore, we could detect the presence of immunoreactive TGFß1 in the bovine adrenal cortex whereas it was undetectable in the adrenal medulla and in the capsule. We also observed that adrenocortical cells secrete TGFß1 under a latent form together with large amounts of α2-macroglobulin, a protease inhibitor known to be implied in the latency of TGFß1 in serum. Taken together, these observations led us to a working hypothesis, proposing TGFß1 as an autocrine and/or paracrine regulator of adrenocortical steroidogenic functions. This concept points out the physiological activation of the latent TGFß1 complex as the important limiting step controlling its action in the adrenal cortex.

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