Androgens regulate aromatase cytochrome P450 messenger ribonucleic acid in rat brain
- PMID: 8013375
- DOI: 10.1210/endo.135.1.8013375
Androgens regulate aromatase cytochrome P450 messenger ribonucleic acid in rat brain
Abstract
The conversion of androgens to estrogens by aromatase cytochrome P450 (P450AROM) is an important step in the mechanism of androgen action in the brain. In adult rats, P450AROM activity (AA) is regulated by androgens in the preoptic area and medial basal hypothalamus, but is constitutive in the amygdala. This study was undertaken to determine the distribution of P450AROM messenger RNA (mRNA) and AA in adult rat brain and examine the effects of steroid treatments on their concentrations in various brain regions. AA was determined by a sensitive assay that measures the production of 3H2O during the conversion of [1 beta-3H]androstenedione to estrone. P450AROM mRNA was measured by a ribonuclease protection assay using a RNA probe complementary to the 5'-coding region of rat P450AROM mRNA. The 32P-labeled P450AROM probe protected two mRNA fragments in brain tissues that expressed AA (preoptic area, medial basal hypothalamus, amygdala, and hippocampus). The larger protected RNA fragment was 430 nucleotides (nt) long and corresponded in size to the full-length protected complementary RNA, whereas the shorter protected RNA fragment was 300 nt long. Brain tissues that did not exhibit AA contained either the smaller protected RNA fragment (cingulate and parietal cortex) or no protected RNA (cerebellum). These results suggest that the 430-nt protected RNA fragment represents mRNA that encodes the functional P450AROM enzyme. In agreement with this conclusion, we found that immature rat ovaries that were stimulated with PMSG to synthesize estrogen contained only the 430-nt protected fragment. The levels of the 430-nt protected RNA fragment differed significantly between brain regions (amygdala > > preoptic area > medial basal hypothalamus > or = hippocampus) and were significantly correlated with AA (r = 0.994; P < 0.001). After castration, the concentrations of P450AROM mRNA and AA decreased significantly in the preoptic area and medial basal hypothalamus (P < 0.05), but not in the amygdala. Treatments with testosterone or dihydrotestosterone maintained P450AROM mRNA and AA at levels approximating those found in intact males. Although 17 beta-estradiol treatment increased AA in the preoptic area, it did not affect the P450AROM mRNA content. These results suggest that the increase in AA observed after exposure to androgens results from regulation of the transcription and/or stability of P450AROM mRNA. In contrast, estradiol appears to exert an effect on AA at the posttranscriptional level.(ABSTRACT TRUNCATED AT 400 WORDS)
Similar articles
-
Distribution of aromatase cytochrome P450 messenger ribonucleic acid in adult rhesus monkey brains.Biol Reprod. 1997 Oct;57(4):772-7. doi: 10.1095/biolreprod57.4.772. Biol Reprod. 1997. PMID: 9314579
-
Regulation of aromatase gene expression in the adult rat brain.Brain Res Bull. 1997;44(4):351-7. doi: 10.1016/s0361-9230(97)00214-1. Brain Res Bull. 1997. PMID: 9370199
-
Anatomic distribution and regulation of aromatase gene expression in the rat brain.Biol Reprod. 1998 Jan;58(1):79-87. doi: 10.1095/biolreprod58.1.79. Biol Reprod. 1998. PMID: 9472926
-
Molecular aspects of brain aromatase cytochrome P450.J Steroid Biochem Mol Biol. 1997 Apr;61(3-6):375-80. J Steroid Biochem Mol Biol. 1997. PMID: 9365213 Review.
-
Aromatase expression in male germ cells.J Steroid Biochem Mol Biol. 2001 Dec;79(1-5):203-8. doi: 10.1016/s0960-0760(01)00137-6. J Steroid Biochem Mol Biol. 2001. PMID: 11850226 Review.
Cited by
-
A role for the androgen metabolite, 5alpha androstane 3beta, 17beta diol (3β-diol) in the regulation of the hypothalamo-pituitary-adrenal axis.Front Endocrinol (Lausanne). 2011 Nov 10;2:65. doi: 10.3389/fendo.2011.00065. eCollection 2011. Front Endocrinol (Lausanne). 2011. PMID: 22649380 Free PMC article.
-
Aromatase cytochrome P450 enzyme expression in human pituitary.Pituitary. 2008;11(1):29-35. doi: 10.1007/s11102-007-0065-3. Pituitary. 2008. PMID: 17703364
-
Ontogeny of cytochrome p450 aromatase mRNA expression in the developing sheep brain.J Neuroendocrinol. 2012 Mar;24(3):443-52. doi: 10.1111/j.1365-2826.2011.02260.x. J Neuroendocrinol. 2012. PMID: 22128891 Free PMC article.
-
Steroid 5α-reductase in adult rat brain after neonatal dihydrotestosterone administration.Neurochem Res. 2013 Mar;38(3):557-63. doi: 10.1007/s11064-012-0948-1. Epub 2012 Dec 11. Neurochem Res. 2013. PMID: 23229791
-
Chronic exposure to anabolic androgenic steroids alters activity and synaptic function in neuroendocrine control regions of the female mouse.Neuropharmacology. 2011 Sep;61(4):653-64. doi: 10.1016/j.neuropharm.2011.05.008. Epub 2011 May 27. Neuropharmacology. 2011. PMID: 21645530 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Research Materials