Biomaterial Database

Regulation of 3 beta-hydroxysteroid dehydrogenase in adrenocortical cells: effects of angiotensin-II and transforming growth factor beta. 1991

W E Rainey, and D Naville, and J I Mason

Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas 75235.

The maintenance of optimal steroidogenesis in adrenocortical cells primarily depends on the chronic action of ACTH to promote the synthesis of the various steroid metabolizing enzymes. In the steroidogenic pathway, the ratio of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) to 17 alpha-hydroxylase cytochrome P450 (P-450(17 alpha)) plays a key role in determining the final steroid products released by adrenal cells. The differences in these enzymes are particularly important when one considers the adrenal zones and the secretion of the zone-specific steroids. In the present study we have investigated the regulation of 3 beta HSD with regard to its enzyme activity, levels of protein and changes in specific mRNA encoding for this enzyme. Following eight days in primary culture, bovine adrenocortical (BAC) cells were found to respond to both ACTH and Bu2 cAMP by increased cortisol production. In addition, 3 beta HSD activity, enzyme protein and mRNA levels were increased in response to both factors. The increases varied from 2-fold for activity to 5-7 fold for mRNA. ACTH and Bu2cAMP also greatly increased P-450(17 alpha) from the near undetectable levels in control cells. In order to examine the possibility of differential regulation of these adrenal steroidogenic enzymes we determined the effects of angiotensin II (A-II) and transforming growth factor beta (TGF beta) on the levels of these enzymes. Both of these factors decreased the ACTH-stimulated levels of P-450(17 alpha) enzyme and mRNA to near nondetectable levels observed within control cells. In addition, these compounds inhibited the ACTH induction of 3 beta HSD. While the mechanism of TGF beta action is not clear, A-II probably is acting through protein kinase C. Indeed the protein kinase C activating phorbol ester, TPA, mimicked the inhibitory effects of A-II on 3 beta HSD and P450(17 alpha). It is important to point out, however, that the effects of A-II and TGF beta on P450(17 alpha) activity appeared more pronounced than their action of 3 beta HSD. This observation may relate to the relative stability of 3 beta HSD as compared to P450(17 alpha). Taken together these data indicate that, while A-II and TGF beta each decrease the levels of steroid-metabolizing enzymes, a differential regulation is observed in that P-450(17 alpha) protein and activity levels are much more sensitive to treatment with these factors.

UI	MeSH Term	Description	Entries
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
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
D005455	Fluorescent Antibody Technique	Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.	Antinuclear Antibody Test, Fluorescent,Coon's Technique,Fluorescent Antinuclear Antibody Test,Fluorescent Protein Tracing,Immunofluorescence Technique,Coon's Technic,Fluorescent Antibody Technic,Immunofluorescence,Immunofluorescence Technic,Antibody Technic, Fluorescent,Antibody Technics, Fluorescent,Antibody Technique, Fluorescent,Antibody Techniques, Fluorescent,Coon Technic,Coon Technique,Coons Technic,Coons Technique,Fluorescent Antibody Technics,Fluorescent Antibody Techniques,Fluorescent Protein Tracings,Immunofluorescence Technics,Immunofluorescence Techniques,Protein Tracing, Fluorescent,Protein Tracings, Fluorescent,Technic, Coon's,Technic, Fluorescent Antibody,Technic, Immunofluorescence,Technics, Fluorescent Antibody,Technics, Immunofluorescence,Technique, Coon's,Technique, Fluorescent Antibody,Technique, Immunofluorescence,Techniques, Fluorescent Antibody,Techniques, Immunofluorescence,Tracing, Fluorescent Protein,Tracings, Fluorescent Protein
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
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
D000324	Adrenocorticotropic Hormone	An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).	ACTH,Adrenocorticotropin,Corticotropin,1-39 ACTH,ACTH (1-39),Adrenocorticotrophic Hormone,Corticotrophin,Corticotrophin (1-39),Corticotropin (1-39),Hormone, Adrenocorticotrophic,Hormone, Adrenocorticotropic
D000804	Angiotensin II	An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME. The amino acid in position 5 varies in different species. To block VASOCONSTRICTION and HYPERTENSION effect of angiotensin II, patients are often treated with ACE INHIBITORS or with ANGIOTENSIN II TYPE 1 RECEPTOR BLOCKERS.	Angiotensin II, Ile(5)-,Angiotensin II, Val(5)-,5-L-Isoleucine Angiotensin II,ANG-(1-8)Octapeptide,Angiotensin II, Isoleucine(5)-,Angiotensin II, Valine(5)-,Angiotensin-(1-8) Octapeptide,Isoleucine(5)-Angiotensin,Isoleucyl(5)-Angiotensin II,Valyl(5)-Angiotensin II,5 L Isoleucine Angiotensin II,Angiotensin II, 5-L-Isoleucine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D013254	Steroid 17-alpha-Hydroxylase	A microsomal cytochrome P450 enzyme that catalyzes the 17-alpha-hydroxylation of progesterone or pregnenolone and subsequent cleavage of the residual two carbons at C17 in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP17 gene, generates precursors for glucocorticoid, androgen, and estrogen synthesis. Defects in CYP17 gene cause congenital adrenal hyperplasia (ADRENAL HYPERPLASIA, CONGENITAL) and abnormal sexual differentiation.	17 alpha-Hydroxylase,17,20-Lyase,CYP17,Cytochrome P-450(17 alpha),P450(c17),Steroid 17 alpha-Monooxygenase,Steroid 17-Hydroxylase,Steroid 17-Monooxygenase,17 alpha-Hydroxylase Cytochrome P-450,17 alpha-Hydroxyprogesterone Aldolase,17,20-Desmolase,Cytochrome P-450(17-alpha),Cytochrome P450(17 alpha),Hydroxyprogesterone Aldolase,Steroid 17 alpha-Hydroxylase,Steroid-17-Hydroxylase,17 alpha Hydroxylase,17 alpha Hydroxylase Cytochrome P 450,17 alpha Hydroxyprogesterone Aldolase,17 alpha-Hydroxylase, Steroid,17 alpha-Monooxygenase, Steroid,17,20 Desmolase,17,20 Lyase,17-Hydroxylase, Steroid,17-Monooxygenase, Steroid,17-alpha-Hydroxylase, Steroid,Aldolase, 17 alpha-Hydroxyprogesterone,Aldolase, Hydroxyprogesterone,Steroid 17 Hydroxylase,Steroid 17 Monooxygenase,Steroid 17 alpha Hydroxylase,Steroid 17 alpha Monooxygenase,alpha-Hydroxyprogesterone Aldolase, 17,alpha-Monooxygenase, Steroid 17