Transforming growth factor beta 1: an autocrine regulator of adrenocortical steroidogenesis.
Transforming growth factor beta 1 (TGF beta 1) is a member of a large family of structurally related regulatory polypeptides which comprises both functionally similar (TGF beta 1, TGF beta 2, TGF beta 3, TGF beta 4 and TGF beta 5) and functionally distinct proteins. In the past few years, TGF beta 1 has emerged as a multifunctional protein. One of its remarkable properties is its capacity to negatively modulate the differentiated, steroidogenic adrenocortical functions. We present here a review of the results from our recent work related to the effects of TGF beta 1 on bovine adrenocortical cell (zona fasciculata-reticularis) functions. We identified the steroid 17 alpha-hydroxylase (P-450 17 alpha) biosynthetic enzyme and the angiotensin II receptor as major targets whose expression are negatively regulated by TGF beta 1 in these cells. We characterized TGF beta 1 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 TGF beta 1 in the bovine adrenal cortex whereas it was undetectable in the adrenal medulla and in the capsule. We also observed that adrenocortical cells secrete TGF beta 1 under a latent form together with large amounts of alpha 2-macroglobulin, a protease inhibitor known to be implied in the latency of TGF beta in serum. Taken together, these observations led us to a working hypothesis, proposing TGF beta 1 as an autocrine and/or paracrine regulator of adrenocortical steroidogenic functions. This concept points out the physiological activation of the latent TGF beta 1 complex as the important limiting step controlling its action in the adrenal cortex.
Feige
J J
JJ
INSERM Unité 244, Centre d'Etudes Nucléaires, Grenoble, France.
Cochet
C
C
Savona
C
C
Shi
D L
DL
Keramidas
M
M
Defaye
G
G
Chambaz
E M
EM
D000302:Adrenal Cortex / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D002417:Cattle; D006854:Hydrocortisone / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*
D016212:Transforming Growth Factor beta; D006854:Hydrocortisone