Transcriptional Regulation of Steroidogenic Genes: STARD1, CYP11A1 and HSD3B

2009 ◽  
Vol 234 (8) ◽  
pp. 880-907 ◽  
Author(s):  
Holly A. LaVoie ◽  
Steven R. King
Keyword(s):  
Transcriptional Regulation ◽  
Current Knowledge ◽  
Regulatory Protein ◽  
Side Chain ◽  
Combinatorial Regulation ◽  
Cytochrome P450scc ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Steroidogenic Acute Regulatory ◽  
Species Specific

Expression of the genes that mediate the first steps in steroidogenesis, the steroidogenic acute regulatory protein (STARD1), the cholesterol side-chain cleavage enzyme, cytochrome P450scc (CYP11A1) and 3β-hydroxysteroid dehydrogenase/Δ5-Δ4 isomerase (HSD3B), is tightly controlled by a battery of transcription factors in the adrenal cortex, the gonads and the placenta. These genes generally respond to the same hormones that stimulate steroid production through common pathways such as cAMP signaling and common actions on their promoters by proteins such as NR5A and GATA family members. However, there are distinct temporal, tissue and species-specific differences in expression between the genes that are defined by combinatorial regulation and unique promoter elements. This review will provide an overview of the hormonal and transcriptional regulation of the STARD1, CYP11A1 and specific steroidogenic HSD3B genes in the adrenal, testis, ovary and placenta and discuss the current knowledge regarding the key transcriptional factors involved.

scholarly journals Growth Differentiation Factor 9 Reverses Activin A Suppression of Steroidogenic Acute Regulatory Protein Expression and Progesterone Production in Human Granulosa-Lutein Cells

2010 ◽  
Vol 24 (8) ◽  
pp. 1676-1677
Author(s):  
Feng-Tao Shi ◽  
Anthony P. Cheung ◽  
Christian Klausen ◽  
He-Feng Huang ◽  
Peter C. K. Leung
Keyword(s):  
Regulatory Protein ◽  
Hydroxysteroid Dehydrogenase ◽  
Activin A ◽  
Inhibin B ◽  
Steroidogenic Acute Regulatory Protein ◽  
Side Chain ◽  
Progesterone Production ◽  
Chain Cleavage ◽  
Cleavage Enzyme ◽  
Steroidogenic Acute Regulatory

Abstract Background: We have reported that growth differentiation factor (GDF) 9 can enhance activin A (βAβA)-induced inhibin B (αβB) secretion in human granulosa-lutein (hGL) cells, but its effects on steroidogenic acute regulatory protein (StAR), ovarian steroidogenic enzymes, and progesterone production are unknown. We undertook this study to further evaluate GDF9 in this regard. Methods: hGL cells from women undergoing in vitro fertilization treatment were cultured with and without small interfering RNA (siRNA) transfection targeted at inhibin α-subunit or GDF9 before treatment with GDF9, activin A, FSH, or combinations. We compared StAR, P450 side-chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase expression in hGL cells and progesterone levels in culture media after these treatments. mRNA, protein, and hormone levels were assessed with real-time RT-PCR, immunoblotting, and ELISA, respectively. Data were analyzed by ANOVA followed by Tukey’s test. Results: Activin A alone reduced basal and FSH-induced progesterone production by decreasing the expression of StAR protein, which regulates the rate-limiting step in steroidogenesis but not P450 side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase. GDF9 attenuated these activin A effects on StAR and progesterone. After transfection of a-subunit siRNA, activin A level increased (P < 0.001), whereas basal and activin A-induced inhibin B levels (with and without GDF9) decreased. Furthermore, the effects of GDF9 in reversing activin A suppression of progesterone production were attenuated (P < 0.001). Transfection of GDF9 siRNA decreased GDF9 as expected and led to lower StAR expression and progesterone secretion than those observed with activin A treatment alone. Conclusion: GDF9 attenuates the suppressive effects of activin A on StAR expression and progesterone production by increasing the expression of inhibin B, which acts as an activin A competitor.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Rare defects in adrenal steroidogenesis

2018 ◽  
Vol 179 (3) ◽  
pp. R125-R141 ◽  
Author(s):  
Walter L Miller
Keyword(s):  
Genetic Disorders ◽  
Regulatory Protein ◽  
Hydroxylase Deficiency ◽  
Rare Mutations ◽  
Chain Cleavage ◽  
Adrenal Steroidogenesis ◽  
Cleavage Enzyme ◽  
Different Populations ◽  
Steroidogenic Acute Regulatory ◽  
21 Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is a group of genetic disorders of adrenal steroidogenesis that impair cortisol synthesis, with compensatory increases in ACTH leading to hyperplastic adrenals. The term ‘CAH’ is generally used to mean ‘steroid 21-hydroxylase deficiency’ (21OHD) as 21OHD accounts for about 95% of CAH in most populations; the incidences of the rare forms of CAH vary with ethnicity and geography. These forms of CAH are easily understood on the basis of the biochemistry of steroidogenesis. Defects in the steroidogenic acute regulatory protein, StAR, disrupt all steroidogenesis and are the second-most common form of CAH in Japan and Korea; very rare defects in the cholesterol side-chain cleavage enzyme, P450scc, are clinically indistinguishable from StAR defects. Defects in 3β-hydroxysteroid dehydrogenase, which also causes disordered sexual development, were once thought to be fairly common, but genetic analyses show that steroid measurements are generally unreliable for this disorder. Defects in 17-hydroxylase/17,20-lyase ablate synthesis of sex steroids and also cause mineralocorticoid hypertension; these are common in Brazil and in China. Isolated 17,20-lyase deficiency can be caused by rare mutations in at least three different proteins. P450 oxidoreductase (POR) is a co-factor used by 21-hydroxylase, 17-hydroxylase/17,20-lyase and aromatase; various POR defects, found in different populations, affect these enzymes differently. 11-Hydroxylase deficiency is the second-most common form of CAH in European populations but the retention of aldosterone synthesis distinguishes it from 21OHD. Aldosterone synthase deficiency is a rare salt-losing disorder. Mild, ‘non-classic’ defects in all of these factors have been described. Both the severe and non-classic disorders can be treated if recognized.

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