Steroidogenesis, StAR and PBR: is there light at the end of the tunnel?
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
M R Waterman
Publications and source records attributed to M R Waterman.
Lanosterol 14alpha-demethylase (CYP51) and spermatogenesis.
CYP51 is the only gene of the cytochrome P450 (P450, or CYP) superfamily that is expressed in prokaryotes and eukaryotes. In animals, the gene product, P45014DM, catalyzes the lanosterol 14alpha-demethylase reaction, an essential step in cholesterol biosynthesis. P45014DM serves a housekeeping role, and it was surprising to find the highest level of CYP51 expression in the testes. This is a result of very high-level CYP51 expression in postmeiotic, haploid spermatids and results in elevated P45014DM activity in these cells. It is proposed that the elevated level of 14alpha-demethylase activity leads to production of signaling sterols by haploid germ cells, although the function of such sterols in males is unknown.
Animals↗
The homeodomain protein Pbx1 is involved in cAMP-dependent transcription of human CYP17.
Pbx1 is a homeodomain transcription factor involved in cAMP-dependent transcriptional regulation of the bovine CYP17 gene. In this study, we have investigated the involvement of Pbx1 in the transcriptional regulation of the human CYP17 gene. Although a sequence identical to previously determined Pbx-binding sites is not present in the promoter region of the human CYP17 gene, three putative Pbx-binding sites are identified by sequence similarity analysis. Coexpression of Pbx1 and a catalytic subunit of protein kinase A (PKA) greatly enhances reporter gene transcription via the 5'-flanking region of the human CYP17 gene. Upon gel shift analysis utilizing nuclear extracts from human adrenal H295R cells, one of the three putative Pbx1-binding sites, -250/-241 bp, shows the typical intense doublet observed with other Pbx-binding sites. 5'-Deletion analyses of the reporter construct containing this Pbx-binding site showed approximately sixfold induction by coexpression of Pbx1 and PKA compared to the basal transcription, suggesting that Pbx1 binds the -250/-241 bp sequence and participates in cAMP-dependent regulation of the human CYP17 gene.
Adrenal Glands↗
Escherichia coli flavodoxin sepharose as an affinity resin for cytochromes P450 and use to identify a putative cytochrome P450c17/3beta-hydroxysteroid dehydrogenase interaction.
Flavodoxin Sepharose (Fld Sepharose), a reagent originally developed to demonstrate an interaction between native Escherichia coli Fld and cytochrome P450c17, has been synthesized, using highly expressed (7 micromol Fld/liter E. coli culture) recombinant E. coli Fld, for use as an affinity resin for microsomal cytochromes P450. As a test of the specificity of Fld Sepharose, we have examined the utility of this resin for purification of P450c17 and P450c21 from a relatively crude mixture of solubilized adrenocortical microsomal proteins. Chromatography of this mixture on Fld Sepharose resulted in a threefold enrichment of cytochrome P450 specific content without spectrally detectable P450 denaturation. Electrophoretic and immunoblot analyses of fractions eluted from the Fld Sepharose column revealed the presence of P450c17 and P450c21, both of which were sufficiently pure, after SDS-PAGE, for identification by N-terminal sequence analysis. Intriguingly, a major protein copurifying with P450c17 and P450c21 was identified as 3beta-hydroxysteroid dehydrogenase (3beta-HSD) which was subsequently found not to directly bind Fld Sepharose. Purified bovine 3beta-HSD covalently linked to Sepharose can bind recombinant bovine P450c17, an interaction which is partially disrupted upon mild heat denaturation of P450c17 or by the nonionic detergent Emulgen. This interaction, however, does not appear to affect P450c17 hydroxylase and lyase activities as measured in vitro. From these results, we propose that 3beta-HSD and P450c17 may associate, perhaps as part of a steroidogenic complex, in the endoplasmic reticulum.
3-Hydroxysteroid Dehydrogenases↗
Negatively charged anabaena flavodoxin residues (Asp144 and Glu145) are important for reconstitution of cytochrome P450 17alpha-hydroxylase activity.
Catalysis by microsomal cytochromes P450 requires the membrane-bound enzyme NADPH-cytochrome P450 reductase (P450 reductase), which transfers electrons to the P450 heme via a flavodoxin-like domain. Previously, we reported that Escherichia coli flavodoxin (Fld), a soluble electron transfer protein, directly interacts with bovine cytochrome P450 17alpha-hydroxylase/17,20-lyase (P450c17) and donates electrons to this enzyme when reconstituted with NADPH-ferredoxin (flavodoxin) reductase (FNR) (Jenkins, C. M., and Waterman, M. R. (1994) J. Biol. Chem. 269, 27401-27408). To investigate whether flavodoxins can serve as useful models of the analogous domain in P450 reductase, we have examined the FNR-Fld system from the cyanobacterium Anabaena. Mutagenesis of two acidic Anabaena Fld residues (D144A and E145A) significantly decreased flavodoxin-supported P450c17 progesterone 17alpha-hydroxylase activity. Specifically, D144A exhibited only 15% of the activity of wild-type Fld, whereas the adjacent mutation, E145A, caused a 40% loss in activity. P450-dependent hydrogen peroxide/superoxide production by wild-type FNR-Fld was measurably higher than that generated by FNR-D144A or FNR-E145A, indicating that the mutations do not lead to P450 heme-mediated electron uncoupling. Interestingly, the D144A and E145A mutants bind with equal or even greater affinity to P450c17 than wild-type Fld. Furthermore, these mutations (D144A and E145A) actually increased cytochrome c reductase activity (35 and 100% higher than wild type). Anabaena Fld residues Asp144 and Glu145 align closely with rat P450 reductase residue Asp208, which has been shown by mutagenesis to be important in electron transfer to P4502B1 but not to cytochrome c (Shen, A. L., and Kasper, C. B. (1995) J. Biol. Chem. 270, 27475-27480). Thus, these residues in flavodoxins and P450 reductase appear to have similar functions in P450 recognition and/or electron transfer, supporting the hypothesis that flavodoxins represent valid models for the FMN-binding domain of P450 reductase.
Amino Acid Sequence↗
Sequence and developmental expression of Cyp18, a member of a new cytochrome P450 family from Drosophila.
Preliminary studies of a partial cDNA clone of the Eig17-1 gene from Drosophila melanogaster have shown that it encodes a probable cytochrome P450 of unknown function. To further characterize the Eig17-1 gene product, a full-length cDNA clone was isolated from a late-larval cDNA library and sequenced. Eig17-1 encodes a protein of 538 amino acids. The predicted protein is a cytochrome P450 that has been assigned to a new family, CYP18. The CYP18 protein is most closely related to steroid and xenobiotic metabolizing P450s of family CYP2 (30-33% identity), and to vertebrate steroidogenic P450s of families CYP17 and CYP21 (25-28% identity). Developmental Northern blot analysis revealed five distinct periods of Cyp18 expression during postembryonic development. Each period lasted 12-15 h, and was tightly correlated with reported ecdysteroid pulses in the first, second and third larval instars, at the time of pupariation and in pupae. This pattern of expression is consistent with the known induction of Cyp18 transcription by 20-hydroxyecdysone at the time of pupariation and suggests that ecdysteroids are major regulators of Cyp18 expression throughout postembryonic development. Northern blot analysis of RNA isolated from different prepupal tissues indicates that Cyp18 is differentially expressed in various ecdysteroid-responsive tissues. High Cyp18 expression was observed in body wall and gut while negligible expression was observed in salivary glands and fat body.
Amino Acid Sequence↗
Expression, purification, and enzymatic properties of recombinant human cytochrome P450c27 (CYP27).
A large number of microsomal P450s have been expressed in Escherichia coli in quantities sufficient for structure/function analysis. However, only one mitochondrial P450 has been successfully overexpressed, that being cholesterol side chain cleavage cytochrome P450 (P450scc). We report here overexpression, purification, and characterization of a second mitochondrial P450, human sterol C-27 hydroxylase (P450c27). The conditions used for expression are very similar to those applied for P450scc, although a quite different purification protocol was necessary to achieve highly purified P450c27. The catalytic properties of purified recombinant human P450c27 resemble those of purified, endogenous rat and rabbit P450c27, regarding both specificity and turnover numbers. Like endogenous P450c27 from rat and rabbit liver, human recombinant P450c27 is only functional in the presence of adrenodoxin and adrenodoxin reductase and shows no activity in the presence of the microsomal P450 reductase. We conclude that P450c27 is most likely not the 1alpha-hydroxylase of 25-hydroxyvitamin D3, contrary to a previous suggestion (Axen, E., Postlind, H., Sjöberg, H., and Wikvall, K. (1994) Proc. Natl. Acad. Sci. USA 91, 10014-10018) because this activity of P450c27 (28 pmol/min/nmol P450) seems far too low to be physiologically relevant. This activity is 10(3) times lower than the 27-hydroxylase activity toward 5beta-cholestane-3alpha,7alpha,12alpha-triol and 40 times lower than the 27-hydroxylation of cholesterol by this enzyme. The development of this expression system and purification procedure creates the potential for structure/function analysis of P450c27, including possible crystallization of this important enzyme.
Amino Acid Sequence↗
cAMP-dependent transactivation involving the homeodomain protein Pbx1.
Pbx1 is a DNA-binding homeodomain protein originally discovered in the t(1;19) chromosomal translocation associated with pediatric pre-B acute lymphoblastic leukemia. Previously we reported a cAMP-regulatory sequence (CRS1) in the promoter region of the bovine CYP17 gene encoding steroid 17alpha-hydroxylase cytochrome P450 (P450c17) to be the first endogenous Pbx1 binding site and that overexpression of Pbx1 in mouse adrenal Y1 tumor cells enhances cAMP-dependent transcription mediated by this element. Here we report further characterization of Pbx1 binding site in CRS1 and role of Pbx1 in cAMP-dependent, CRS1-mediated transcription. By gel shift analysis utilizing nuclear extracts from Y1 cells, a high-affinity Pbx-binding sequence has been determined to be TTGAT(T/G)GA(T/C)A which represents the 5' portion of CRS1. An artificial Pbx-binding sequence (PRS), previously determined by random PCR analysis, is similar to the Pbx1-binding sequence in CRS1 and by both gel shift analysis and transfection studies shows characteristics very similar to CRS1. Upon overexpression, Pbx1 is found capable of enhancing CRS1-mediated transcription in both steroidogenic (Y1, JEG3) and nonsteroidogenic (HepG2 and S194) cells when coexpressed with the catalytic subunit of cAMP-dependent protein kinase A. Thus even though Pbx1 has been found to be involved only in cAMP-dependent transcription of a gene involved in steroidogenesis (CYP17), Pbx1 is capable of participating in cAMP-dependent transcription of target genes without complex formation with steroidogenic tissue-specific nuclear factors.
Adrenal Glands↗
Cytochromes P450 12: diversity of ACTH (cAMP)-dependent transcription of bovine steroid hydroxylase genes.
An essential role of ACTH is to assure that optimal steroidogenic capacity is maintained in the adrenal cortex throughout life. This is achieved by maintaining transcriptional pressure on the genes encoding the adrenocortical steroid hydroxylases via the second messenger, cAMP. Even though these genes respond coordinately to cAMP, it has been surprising to discover that each gene uses its own unique cAMP response system during this coordinate response. Thus, different cis elements and sets of transcription factors control the cAMP responsiveness of each different steroid hydroxylase gene. Although the physiological basis of this diversity in biochemical mechanisms of transcriptional regulation is not apparent, a portion of this signaling pathway is common to all of these genes. In particular, the action of cAMP-dependent protein kinase and an as yet uncharacterized cycloheximide-sensitive step are necessary for ACTH-mediated transcription of each gene. Biochemical characterization of these common steps in the ACTH-dependent signaling pathways is essential to an understanding of the maintenance of optimal steroidogenic capacity in the adrenal cortex.
Adrenocorticotropic Hormone↗
Developmentally regulated expression and activity of 17alpha-hydroxylase/C-17,20-lyase cytochrome P450 in rat liver.
We have investigated the developmental pattern of expression and activity of 17alpha-hydroxylase/C-17,20-lyase cytochrome P450 (cytochrome P450c17) in the liver, stomach, duodenum, and testis of rats from day 18 of pregnancy to adulthood. In the male liver, the enzyme became detectable at birth (135 pmol/mg protein x min) at a level comparable to that in the testis (188 pmol/mg protein x min). The activity then increased dramatically, reaching a peak at 8 days (691 pmol/mg protein x min), which was more than 4-fold the testicular levels in rats of the same age or in adults. Thereafter it declined steadily, becoming undetectable from puberty onward. The hepatic peak followed a depression in testicular activity (58 pmol/mg protein x min) on day 6. Northern and immunoblot analyses showed a good temporal correlation between enzyme activity and the occurrence of P450c17 messenger RNA (mRNA) and protein. The same patterns of mRNA and protein occurrence were observed in female rat liver, indicating that the hepatic CYP17 expression is not sexually dimorphic. Sequencing confirmed a complete identity in the coding region between hepatic and gonadal mRNAs. Hepatic P450c17 mRNA, however, was 150-200 bases longer than the gonadal counterparts. No significant expression of mRNAs encoding P450scc and P450arom was observed in liver of either sex at any age. In stomach and duodenum, enzyme activity was much lower (maxima at 25 and 14 pmol/mg protein x min, respectively) than that in liver, but persisted from the time of weaning onward. It is suggested that the hepatic peak in P450c17 activity may serve to convert circulating progestogens into androgens for gonadal aromatization during Sertoli and granulosa cell proliferation.
Androgens↗
Structure and mapping of the human lanosterol 14alpha-demethylase gene (CYP51) encoding the cytochrome P450 involved in cholesterol biosynthesis; comparison of exon/intron organization with other mammalian and fungal CYP genes.
Sterol 14alpha-demethylase (P45014DM) encoded by CYP51 is a member of the cytochrome P450 (CYP) gene superfamily involved in sterol biosynthesis in fungi, plants, and animals. Constraints imposed by the specific function of CYP51 have severely limited sequence divergence in this family. Consequently, CYP51 is the only P450 family recognizable across all eukaryotic phyla. We have determined the structure of the functional human CYP51 gene, which spans 22 kb, is divided into 10 exons, and maps to 7q21.2-q21.3. The 5' portion of intron 1 is GC-rich and contains potential binding sites for several transcription factors. Primer extension studies reveal predominant transcription initiation sites in liver, kidney, lung, and placenta 250 and 249 bp upstream from the translation start site and a second major site at -100 bp. Ubiquitous expression of human CYP51 (Strömstedt et al., Arch. Biochem. Biophys. 329: 73-81, 1996), the absence of TATA and CAAT patterns, a GC-rich sequence in the promoter region, and initiation of CYP51 transcription at more than one site indicate that CYP51 is a housekeeping gene. The 5'-flanking region, exon 1, and a portion of intron 1 show the characteristics of a CpG island, with the observed/expected CpG ratio of 0.79. Sterol responsive element-like motifs were present in this region, suggesting regulation by oxysterols via a mechanism similar to that associated with other genes involved in cholesterol homeostasis. Comparison of the human CYP51 gene structure with structures of other mammalian and fungal CYP gene families shows that 7 of the 9 CYP51 introns are located at unique positions. More than 80 intron locations exist in mammalian and fungal CYP gene families, and it seems very unlikely that all these introns could have been present in the primordial CYP gene.
Amino Acid Sequence↗
Studies of distant members of the P450 superfamily (P450scc and P450c27) by random chimeragenesis.
"Random chimeragenesis" (Kim, J.-Y., and Devreotes, P. N. (1994) J. Biol. Chem. 269, 28724-28731; Levin, L. R., and Reed, R. R. (1995) J. Biol. Chem. 270, 7573-7579) has been used to generate chimeras between two distant P450s involved in catabolism of cholesterol in mammals, P450scc (product of CYP11A1 gene) and P450c27 (product of CYP27 gene). Both are mitochondrial P450s which hydroxylate the side chain of cholesterol. Even though these P450s are only about 25% identical, we wondered whether their similar substrate specificity might permit mapping of the active sites by this technique. Four chimeric DNAs encoding three different proteins have been obtained testifying that short stretches of nucleotide identity (six nucleotides preceding the crossover point) are sufficient for homologous recombination in Escherichia coli, the basis of the random chimeragenesis technique. The N-terminal part of the chimeras was formed by P450scc and the C-terminus was from P450c27. The chimeric P450s have been expressed in E. coli and partially purified. Though they displayed a peak at 453 nm in their CO-difference spectra, indicating that the proteins are properly folded and hemin is correctly incorporated, none of the chimeras had detectable catalytic activity with either cholesterol (substrate for P450scc) or 5beta-cholestane-3alpha,7alpha,12alpha-triol (substrate for P450c27). To investigate whether the chimeras bind substrate, titrations with 22R-hydroxycholesterol have been carried out. Addition of 22R-hydroxycholesterol to recombinant P450scc which is in the low spin form leads to conversion to the high spin form. Titration of chimeras with 22R-hydroxycholesterol did not result in their conversion to the high spin form. However, a shift to 426-430 nm was observed in the difference spectrum of two of the chimeras with a minimum around 406 nm. Thus, addition of 22R-hydroxycholesterol to these chimeras results in binding of the steroid in the enzyme active site and conversion of one low spin form to a different low spin form. Possible explanations for the absence of enzymatic activity and the potential advantages of the random chimeragenesis technique to generate chimeras between different P450s are discussed.
Amino Acid Sequence↗
The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family.
The three human lanosterol 14 alpha-demethylase (CYP51) genes have been mapped to human chromosomes 3, 7, and 13 using a polychromosomal somatic cell hybrid panel. Two of the genes have been cloned from human chromosome 3-specific (CYP51P1) or from human chromosome 13-containing (CYP51P2) cell hybrids. Both were found to be processed pseudogenes, the first reported in the cytochrome P450 (CYP) gene superfamily. The functional CYP51 gene resides on human chromosome 7. CYP51P1 is 96.5% identical to the human CYP51 coding sequence and is not interrupted with introns but has six in-frame stop codons resulting from point mutations. The intronless CYP51P2 gene is 97.2% identical to the CYP51 cDNA coding region. It has a 1-bp insertion leading to a change of reading frame after codon 9 and a stop codon after amino acid 81. In addition, the CYP51P2 sequence is interrupted with a 5' truncated 131-bp LINE-1 element after nucleotide 606. The element belongs to the youngest LINE subfamily Sb and is 98.2% identical to the LINE-1 element expressed in human teratocarcinoma cells. CYP51 processed pseudogenes are the only known examples of the reverse flow of genetic information during evolution of the large (more than 480 genes) CYP superfamily, suggesting expression in the germ line and a housekeeping function of the lanosterol 14 alpha-demethylase gene. CYP51 pseudogenes evolved by two independent reverse transcription events of the human CYP51 mRNA approximately 9.5 MYR (CYP51P2) and approximately 11.7 MYR (CYP51P1) ago and were inactivated soon after the insertion. The truncated L1 element was inserted into CYP51P2 approximately 6 MYR ago.
Amino Acid Sequence↗
The interaction of NADPH-P450 reductase with P450: an electrochemical study of the role of the flavin mononucleotide-binding domain.
The electrochemically reduced mediator cobalt sepulchrate requires the presence of a flavoprotein for the rapid transfer of electrons to cytochrome P450. This electrochemical method has been used here to show the interaction of NADPH-P450 reductase (either the detergent-solubilized form, d-OR, or the proteolytic-cleaved truncated form, t-OR), as well as Escherichia coli flavodoxin (FLD), with P450c17 by measuring the rate of 17 alpha-hydroxylation of progesterone. When NADPH is used as electron donor with a reconstituted system composed of d-OR and P450c17, the addition of t-OR, flavodoxin, or cytochrome c inhibited the rate of formation of 17 alpha-hydroxyprogesterone. These results suggest the presence of a common protein binding site on the surface of d-OR, t-OR, and flavodoxin which plays a role in the interaction of the flavoproteins with the P450. It is speculated that a domain composed of acidic amino acids, located near the flavin mononucleotide-binding region of the flavoproteins, may serve as this site. No inhibition by t-OR, flavodoxin, or cytochrome c is observed when comparable experiments are carried out using the artificial recombinant fusion protein rF450[mBov17A/mRatOR]L1 containing the heme-domain of P450c17 linked to the flavin-domains of NADPH-P450 reductase.
Amino Acid Sequence↗
The ubiquitously expressed human CYP51 encodes lanosterol 14 alpha-demethylase, a cytochrome P450 whose expression is regulated by oxysterols.
Sterol biosynthesis requires the removal of the 14 alpha-methyl group from lanosterol in animals and fungi and from obtusifoliol in plants. This reaction is catalyzed by a microsomal cytochrome P450, the sterol 14 alpha-demethylase (P450(14DM), which is the only P450 described so far to be expressed in different phyla. A cDNA encoding human P450(14DM) was isolated from a liver cDNA library using a partial rat lanosterol 14 alpha-demethylase cDNA probe. The deduced amino acid sequence is 93% and 38--42% identical to rat and fungal P450(14DM), respectively. Expression of the human CYP51 cDNA in Escherichia coli showed that the cDNA encodes an enzyme having lanosterol 14 alpha-demethylase activity. Northern blot analysis showed that CYP51 mRNA is ubiquitously expressed with highest levels in testis, ovary, adrenal, prostate, liver, kidney, and lung. Many genes involved in cholesterol homeostasis are regulated by cholesterol or its metabolites. In the case of CYP51, cholesterol deprivation led to a 2.6- to 3.8-fold induction of mRNA levels in human adrenocortical H295R cells and this effect was suppressed by the addition of 25-hydroxycholesterol. In human hepatoma HepG2 cells, no effect of cholesterol deprivation was observed; however, the levels of CYP51 mRNA were reduced 4- to 6-fold by the addition of 25-hydroxycholesterol. Thus, like several other genes in the cholesterol biosynthetic pathway, including the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) synthase, HMG CoA reductase, squalene synthase, and farnesyl diphosphate synthase, the expression of the human CYP51 is suppressed by oxysterols.
Amino Acid Sequence↗
Preimplantation mouse blastocysts fail to express CYP genes required for estrogen biosynthesis.
Implantation is initiated on day 4 in the mouse and on day 13 in the pig. The preimplantation pig blastocyst synthesizes steroid hormones, but whether preimplantation rodent embryos also have this ability has remained unresolved for the last two decades. In this study, the mRNAs encoding NADPH-cytochrome P450 reductase (P450-reductase), adrenodoxin, lanosterol 14-demethylase P450 (CYP51), 17 alpha-hydroxylase P450 (CYP17), cholesterol side-chain cleavage P450 (CYP11A1), sterol 27-hydroxylase P450 (CYP27), and aromatase P450 (CYP19) were examined in day 4 mouse blastocysts (day 1 = vaginal plug) and in day 13 and 16 pig blastocysts using reverse transcription-polymerase chain reaction (RT-PCR). In mouse blastocysts, mRNAs of P450-reductase, adrenodoxin, and CYP51, but not CYP17, CYP11A1, CYP27, and CYP19, were detected. In agreement with this finding, no aromatase protein could be detected by immunohistochemistry. By contrast, all these mRNAs were detected in the pig blastocyst. Furthermore, both the ovarian and placental types of aromatase (CYP19) mRNAs were detected in the pig blastocyst on days 13 and 16 of pregnancy, although the ovarian form was more abundant. Both forms of aromatase were much higher in day 13 than in day 16 pig blastocysts. The results provide definitive evidence that the preimplantation mouse blastocyst, as opposed to the pig blastocyst, has no ability to synthesize estrogen and no steroidogenic capacity. Maternal estrogen synthesis is essential for implantation of the mouse blastocyst.
Adrenodoxin↗
Signal transduction pathways combining peptide hormones and steroidogenesis.
Explore the source record for details and available documents.
Cyclic AMP↗
Mechanisms of ACTH(cAMP)-dependent transcription of adrenal steroid hydroxylases.
The action of peptide hormones from the anterior pituitary regulates transcription of a large number of genes located in most, if not all, tissues. This action is mediated through regulation of steroid hormone production in the steroidogenic factories (adrenals, gonads). These steroid hormones are transported through the circulation to the peripheral tissues where they serve as ligands for the family of zinc-finger nuclear receptor transcription factors. The mechanisms by which peptide hormones regulate steroid hormone production include a chronic response mediated by elevated levels of cAMP resulting from the binding of peptide hormones to their cell surface receptors which enhances transcription of the genes encoding steroid hydroxylases required for steroid hormone biosynthesis. The action of ACTH in the adrenal cortex has been studied in greatest detail leading to identification of unique cAMP-response sequences (CRS) in the different bovine steroid hydroxylase genes. Most likely FSH and LH mediate steroid hydroxylase gene expression in the gonads via the same response elements. Unlike developmental/tissue-specific transcription of these genes which is regulated by a common transcription factor (SF-1), cAMP-dependent transcription of each steroid hydroxylase gene requires a different transcription factor.
Adrenal Cortex↗