Biomaterial Database

Type beta transforming growth factor affects adrenocortical cell-differentiated functions. 1987

J J Feige, and C Cochet, and W E Rainey, and C Madani, and E M Chambaz

Laboratoire de Biochimie des Régulations Cellulaires Endocrines, Unité Institut National de la Santé et de la Recherche Médicale 244, Grenoble, France.

Type beta transforming growth factor (TGF-beta) had no detectable effect on mitogenic activities of bovine adrenocortical cells in culture. However, the presence of TGF-beta (1 ng/ml) in the medium resulted in a striking alteration of adrenocortical cell steroidogenic activities, maximally expressed after 18-20 h of treatment. TGF-treated cells exhibited a basal as well as an adrenocorticotropin-stimulated cortisol production inhibition by an average 50-60%, while cAMP accumulation in response to the hormone was not modified. Detailed study of the adrenocortical steroid biosynthetic pathway by high performance liquid chromatography analysis and supply of representative steroid substrates revealed a drastic loss (average 50%) of the steroid 17 alpha-hydroxylase activity following TGF treatment. TGF-beta thus appeared as a potent negative modulator of adrenocortical 17 alpha-hydroxylase activity. This TGF-induced loss in the activity of a key steroidogenic enzyme resulted in a shift of the adrenocortical cell secretion pattern at the expense of the 17 alpha-hydroxysteroid end products. This 17 alpha-hydroxylation alteration was also expressed when TGF-treated cells were challenged by angiotensin II. However, in this case, an additional lesion was suggested by a 70-90% inhibition in angiotensin II-activated cortisol production. This could be explained by the observation that TGF-beta exposure induced an average 50% decrease in the adrenocortical cell angiotensin II receptor number without any detectable change in receptor affinity (Ka approximately 10(9) M-1). In addition, a parallel alteration in the angiotensin II-activated phosphoinositide breakdown was observed in TGF-treated cells, indicating that TGF-beta appears as a negative effector of the adrenocortical cell transmembrane signaling system in the case of angiotensin II. It is concluded that, in vitro, TGF-beta is a potent modulator of differentiated adrenocortical cell functions, in which at least two major negatively regulated specific targets were characterized. The mechanism(s) of action and the possible physiological significance of TGF-beta in the control of the development and the differentiated functions of the adrenocortical gland in vivo remain to be established.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D010716	Phosphatidylinositols	Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.	Inositide Phospholipid,Inositol Phosphoglyceride,Inositol Phosphoglycerides,Inositol Phospholipid,Phosphoinositide,Phosphoinositides,PtdIns,Inositide Phospholipids,Inositol Phospholipids,Phosphatidyl Inositol,Phosphatidylinositol,Inositol, Phosphatidyl,Phosphoglyceride, Inositol,Phosphoglycerides, Inositol,Phospholipid, Inositide,Phospholipid, Inositol,Phospholipids, Inositide,Phospholipids, Inositol
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D002454	Cell Differentiation	Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.	Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D006133	Growth Substances	Signal molecules that are involved in the control of cell growth and differentiation.	Mitogens, Endogenous,Endogenous Mitogens
D006854	Hydrocortisone	The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.	Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol
D000242	Cyclic AMP	An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.	Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000302	Adrenal Cortex	The outer layer of the adrenal gland. It is derived from MESODERM and comprised of three zones (outer ZONA GLOMERULOSA, middle ZONA FASCICULATA, and inner ZONA RETICULARIS) with each producing various steroids preferentially, such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and ANDROSTENEDIONE. Adrenal cortex function is regulated by pituitary ADRENOCORTICOTROPIN.	Cortex, Adrenal