Brain aromatase cytochrome P-450 messenger RNA levels and enzyme activity during prenatal and perinatal development in the rat

Edwin D. Lephart, Evan R. Simpson, Michael J. McPhaul, Michael W. Kilgore, Jean D. Wilson, Sergio Ojeda

    Research output: Contribution to journalArticle

    107 Citations (Scopus)

    Abstract

    Aromatase cytochrome P-450 (P-450AROM) enzyme activity catalyzes the conversion of androgens to estrogens in specific brain areas. During development local estrogen formation is thought to influence the sexual differentiation of neural structures (i.e. increase neurite growth and establish neural circuitry) and modulate reproductive functions. This study was undertaken to investigate the ontogeny of the (P-450AROM) enzyme and its messenger RNA (mRNA) in medial basal hypothalamic (MBH) and preoptic area (POA) tissue during late fetal and perinatal development of the rat. Aromatase activity in the MBH-POA was negligible before gestational day (GD) 16 ( 5.0 pmol/h/mg protein), and then declined to low levels at GD 22 and 2 days post-birth (≈ 1 pmol/h/mg protein). The profile of P-450AROM mRNA in the MBH-POA tissue was characterized by a predominant 2.7 kilobase (kb) mRNA species, similar in size to the largest functional P-450AROM mRNA observed in adult rat ovarian tissue. At GD 15, the P-450AROM mRNA was undetectable; low but detectable levels were seen at GD 17, the abundance increased at later time points and remained at peak levels on GDs 18 through 20, decreased slightly by GD 22, and then declined further by 2 days post-birth. The developmental increase in P-450AROM mRNA levels correlated with the ascending pattern of enzyme activity before GD 19, but the marked decrease in enzyme activity seen after GD 19 was not accompanied by a corresponding decline in mRNA levels. These findings provide evidence for the presence of P-450AROM mRNA in neural tissue and suggest that increases in P-450AROM mRNA levels determine, at least in part, enzymatic activity during the period of development where brain aromatase is increasing. In contrast, the perinatal decline in enzyme activity appears to be regulated by factors that operate via mechanisms other than inhibition of P-450AROM gene expression.

    Original languageEnglish (US)
    Pages (from-to)187-192
    Number of pages6
    JournalMolecular Brain Research
    Volume16
    Issue number3-4
    DOIs
    StatePublished - 1992

    Fingerprint

    Aromatase
    Cytochrome P-450 Enzyme System
    Messenger RNA
    Brain
    Enzymes
    Preoptic Area
    Estrogens
    Parturition
    Sex Differentiation
    Neurites
    Fetal Development
    Androgens
    Proteins
    Gene Expression

    Keywords

    • Aromatase
    • Brain
    • Development
    • Prenatal
    • Rat

    ASJC Scopus subject areas

    • Molecular Biology
    • Cellular and Molecular Neuroscience

    Cite this

    Brain aromatase cytochrome P-450 messenger RNA levels and enzyme activity during prenatal and perinatal development in the rat. / Lephart, Edwin D.; Simpson, Evan R.; McPhaul, Michael J.; Kilgore, Michael W.; Wilson, Jean D.; Ojeda, Sergio.

    In: Molecular Brain Research, Vol. 16, No. 3-4, 1992, p. 187-192.

    Research output: Contribution to journalArticle

    Lephart, Edwin D. ; Simpson, Evan R. ; McPhaul, Michael J. ; Kilgore, Michael W. ; Wilson, Jean D. ; Ojeda, Sergio. / Brain aromatase cytochrome P-450 messenger RNA levels and enzyme activity during prenatal and perinatal development in the rat. In: Molecular Brain Research. 1992 ; Vol. 16, No. 3-4. pp. 187-192.
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    abstract = "Aromatase cytochrome P-450 (P-450AROM) enzyme activity catalyzes the conversion of androgens to estrogens in specific brain areas. During development local estrogen formation is thought to influence the sexual differentiation of neural structures (i.e. increase neurite growth and establish neural circuitry) and modulate reproductive functions. This study was undertaken to investigate the ontogeny of the (P-450AROM) enzyme and its messenger RNA (mRNA) in medial basal hypothalamic (MBH) and preoptic area (POA) tissue during late fetal and perinatal development of the rat. Aromatase activity in the MBH-POA was negligible before gestational day (GD) 16 ( 5.0 pmol/h/mg protein), and then declined to low levels at GD 22 and 2 days post-birth (≈ 1 pmol/h/mg protein). The profile of P-450AROM mRNA in the MBH-POA tissue was characterized by a predominant 2.7 kilobase (kb) mRNA species, similar in size to the largest functional P-450AROM mRNA observed in adult rat ovarian tissue. At GD 15, the P-450AROM mRNA was undetectable; low but detectable levels were seen at GD 17, the abundance increased at later time points and remained at peak levels on GDs 18 through 20, decreased slightly by GD 22, and then declined further by 2 days post-birth. The developmental increase in P-450AROM mRNA levels correlated with the ascending pattern of enzyme activity before GD 19, but the marked decrease in enzyme activity seen after GD 19 was not accompanied by a corresponding decline in mRNA levels. These findings provide evidence for the presence of P-450AROM mRNA in neural tissue and suggest that increases in P-450AROM mRNA levels determine, at least in part, enzymatic activity during the period of development where brain aromatase is increasing. In contrast, the perinatal decline in enzyme activity appears to be regulated by factors that operate via mechanisms other than inhibition of P-450AROM gene expression.",
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