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 R. Ojeda

doi:10.1016/0169-328X(92)90224-Y

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 R. Ojeda

Pharmacology and Nutritional Sciences

Research output: Contribution to journal › Article › peer-review

110 Scopus citations

Abstract

Aromatase cytochrome P-450 (P-450_AROM) 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-450_AROM) 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 (<0.1 pmol/h/mg protein), increased over 10-fold at GD 17 and continued to increase (over 5-fold) to peak levels at GD 19 (> 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-450_AROM 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-450_AROM mRNA observed in adult rat ovarian tissue. At GD 15, the P-450_AROM 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-450_AROM 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-450_AROM mRNA in neural tissue and suggest that increases in P-450_AROM 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-450_AROM gene expression.

Original language	English
Pages (from-to)	187-192
Number of pages	6
Journal	Molecular Brain Research
Volume	16
Issue number	3-4
DOIs	https://doi.org/10.1016/0169-328X(92)90224-Y
State	Published - Dec 1992

Bibliographical note

Funding Information:
Acknowledgements. The skilled editorial assistance of Sandra Finley is gratefully acknowledged. We wish to thank Gary Means for assistance in the preparation of Taq amplified probes. This work was supported by USPHS Grant AG08174 (E.R.S.), HD-09988, Project IV and HD-25123 (S.R.O.) and DK-03892 (J.D.W.). E.D.L. and M.W.K. were supported in part by USPHS Training Grant T32-HD07062. Portions of this work appeared in abstract form at the 1990 meeting of The Endocrine Society.

Funding

Acknowledgements. The skilled editorial assistance of Sandra Finley is gratefully acknowledged. We wish to thank Gary Means for assistance in the preparation of Taq amplified probes. This work was supported by USPHS Grant AG08174 (E.R.S.), HD-09988, Project IV and HD-25123 (S.R.O.) and DK-03892 (J.D.W.). E.D.L. and M.W.K. were supported in part by USPHS Training Grant T32-HD07062. Portions of this work appeared in abstract form at the 1990 meeting of The Endocrine Society.

Funders	Funder number
National Institute on Aging	R01AG008174
U.S. Public Health Service	DK-03892, HD-25123, T32-HD07062, HD-09988, AG08174

Keywords

Aromatase
Brain
Development
Prenatal
Rat

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience

Access to Document

10.1016/0169-328X(92)90224-Y

Cite this

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

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 (<0.1 pmol/h/mg protein), increased over 10-fold at GD 17 and continued to increase (over 5-fold) to peak levels at GD 19 (> 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.",

keywords = "Aromatase, Brain, Development, Prenatal, Rat",

author = "Lephart, {Edwin D.} and Simpson, {Evan R.} and McPhaul, {Michael J.} and Kilgore, {Michael W.} and Wilson, {Jean D.} and Ojeda, {Sergio R.}",

note = "Funding Information: Acknowledgements. The skilled editorial assistance of Sandra Finley is gratefully acknowledged. We wish to thank Gary Means for assistance in the preparation of Taq amplified probes. This work was supported by USPHS Grant AG08174 (E.R.S.), HD-09988, Project IV and HD-25123 (S.R.O.) and DK-03892 (J.D.W.). E.D.L. and M.W.K. were supported in part by USPHS Training Grant T32-HD07062. Portions of this work appeared in abstract form at the 1990 meeting of The Endocrine Society.",

year = "1992",

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doi = "10.1016/0169-328X(92)90224-Y",

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AU - Lephart, Edwin D.

AU - Simpson, Evan R.

AU - McPhaul, Michael J.

AU - Kilgore, Michael W.

AU - Wilson, Jean D.

AU - Ojeda, Sergio R.

N1 - Funding Information: Acknowledgements. The skilled editorial assistance of Sandra Finley is gratefully acknowledged. We wish to thank Gary Means for assistance in the preparation of Taq amplified probes. This work was supported by USPHS Grant AG08174 (E.R.S.), HD-09988, Project IV and HD-25123 (S.R.O.) and DK-03892 (J.D.W.). E.D.L. and M.W.K. were supported in part by USPHS Training Grant T32-HD07062. Portions of this work appeared in abstract form at the 1990 meeting of The Endocrine Society.

PY - 1992/12

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N2 - 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 (<0.1 pmol/h/mg protein), increased over 10-fold at GD 17 and continued to increase (over 5-fold) to peak levels at GD 19 (> 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.

AB - 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 (<0.1 pmol/h/mg protein), increased over 10-fold at GD 17 and continued to increase (over 5-fold) to peak levels at GD 19 (> 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.

KW - Aromatase

KW - Brain

KW - Development

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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