Estrogen and androgen differentially modulate the growth-associated protein GAP-43 (neuromodulin) messenger ribonucleic acid in postnatal rat brain

Paul J. Shughrue, Daniel Dorsa

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The level of expression of the gene encoding GAP-43, a protein implicated in neurite outgrowth and motility, is sexually dimorphic in the postnatal brain and modulated by testosterone (T). To determine which metabolite of T modulates the expression of GAP-43 in the postnatal brain, the present study investigated the effect of estrogen and androgen receptor antagonists, tamoxifen (TAM) and cyproterone acetate (CA), and agonists, diethylstilbestrol (DES) and dihydrotestosterone (DHT). On postnatal day 1, male rats were injected sc daily with oil, TAM, or CA, whereas additional female pups were treated with oil, DES, or DHT. On postnatal day 6, brains were collected and 16-μm cryostat sections processed and hybridized with a 35S-labeled antisense riboprobe complementary to GAP-43 messenger RNA (mRNA). A comparison of hybridization signal in the cerebral cortex, bed nucleus of the stria terminalis, and medial preoptic nucleus demonstrated that the level of GAP-43 mRNA in males was significantly higher than in females. However, when male pups were injected with CA, a female-like level of GAP-43 mRNA was measured in the cerebral cortex. The low level of GAP-43 hybridization signal in the female cortex was markedly increased when females were treated with DHT. In contrast, the level of GAP-43 mRNA in the male medial preoptic nucleus was attenuated after treatment with TAM, whereas the level in the female was augmented with DES. Interestingly, the level of GAP- 43 mRNA in the bed nucleus was reduced when males were treated with either TAM or CA and augmented when females were administered either DES or DHT. The results of these studies indicate that the effects of T on GAP-43 mRNA levels in the postnatal brain are modulated by estrogen- and androgen receptor- mediated events in a region-specific manner.

Original languageEnglish (US)
Pages (from-to)1321-1328
Number of pages8
JournalEndocrinology
Volume134
Issue number3
DOIs
StatePublished - Mar 1994
Externally publishedYes

Fingerprint

GAP-43 Protein
Androgens
Estrogens
RNA
Cyproterone Acetate
Brain
Diethylstilbestrol
Dihydrotestosterone
Tamoxifen
Messenger RNA
Preoptic Area
Cerebral Cortex
Oils
Androgen Receptor Antagonists
Septal Nuclei
Androgen Receptors
Estrogen Receptors
Testosterone
Gene Expression

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Estrogen and androgen differentially modulate the growth-associated protein GAP-43 (neuromodulin) messenger ribonucleic acid in postnatal rat brain. / Shughrue, Paul J.; Dorsa, Daniel.

In: Endocrinology, Vol. 134, No. 3, 03.1994, p. 1321-1328.

Research output: Contribution to journalArticle

@article{4cc532974b924520973673626152c3a9,
title = "Estrogen and androgen differentially modulate the growth-associated protein GAP-43 (neuromodulin) messenger ribonucleic acid in postnatal rat brain",
abstract = "The level of expression of the gene encoding GAP-43, a protein implicated in neurite outgrowth and motility, is sexually dimorphic in the postnatal brain and modulated by testosterone (T). To determine which metabolite of T modulates the expression of GAP-43 in the postnatal brain, the present study investigated the effect of estrogen and androgen receptor antagonists, tamoxifen (TAM) and cyproterone acetate (CA), and agonists, diethylstilbestrol (DES) and dihydrotestosterone (DHT). On postnatal day 1, male rats were injected sc daily with oil, TAM, or CA, whereas additional female pups were treated with oil, DES, or DHT. On postnatal day 6, brains were collected and 16-μm cryostat sections processed and hybridized with a 35S-labeled antisense riboprobe complementary to GAP-43 messenger RNA (mRNA). A comparison of hybridization signal in the cerebral cortex, bed nucleus of the stria terminalis, and medial preoptic nucleus demonstrated that the level of GAP-43 mRNA in males was significantly higher than in females. However, when male pups were injected with CA, a female-like level of GAP-43 mRNA was measured in the cerebral cortex. The low level of GAP-43 hybridization signal in the female cortex was markedly increased when females were treated with DHT. In contrast, the level of GAP-43 mRNA in the male medial preoptic nucleus was attenuated after treatment with TAM, whereas the level in the female was augmented with DES. Interestingly, the level of GAP- 43 mRNA in the bed nucleus was reduced when males were treated with either TAM or CA and augmented when females were administered either DES or DHT. The results of these studies indicate that the effects of T on GAP-43 mRNA levels in the postnatal brain are modulated by estrogen- and androgen receptor- mediated events in a region-specific manner.",
author = "Shughrue, {Paul J.} and Daniel Dorsa",
year = "1994",
month = "3",
doi = "10.1210/en.134.3.1321",
language = "English (US)",
volume = "134",
pages = "1321--1328",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "3",

}

TY - JOUR

T1 - Estrogen and androgen differentially modulate the growth-associated protein GAP-43 (neuromodulin) messenger ribonucleic acid in postnatal rat brain

AU - Shughrue, Paul J.

AU - Dorsa, Daniel

PY - 1994/3

Y1 - 1994/3

N2 - The level of expression of the gene encoding GAP-43, a protein implicated in neurite outgrowth and motility, is sexually dimorphic in the postnatal brain and modulated by testosterone (T). To determine which metabolite of T modulates the expression of GAP-43 in the postnatal brain, the present study investigated the effect of estrogen and androgen receptor antagonists, tamoxifen (TAM) and cyproterone acetate (CA), and agonists, diethylstilbestrol (DES) and dihydrotestosterone (DHT). On postnatal day 1, male rats were injected sc daily with oil, TAM, or CA, whereas additional female pups were treated with oil, DES, or DHT. On postnatal day 6, brains were collected and 16-μm cryostat sections processed and hybridized with a 35S-labeled antisense riboprobe complementary to GAP-43 messenger RNA (mRNA). A comparison of hybridization signal in the cerebral cortex, bed nucleus of the stria terminalis, and medial preoptic nucleus demonstrated that the level of GAP-43 mRNA in males was significantly higher than in females. However, when male pups were injected with CA, a female-like level of GAP-43 mRNA was measured in the cerebral cortex. The low level of GAP-43 hybridization signal in the female cortex was markedly increased when females were treated with DHT. In contrast, the level of GAP-43 mRNA in the male medial preoptic nucleus was attenuated after treatment with TAM, whereas the level in the female was augmented with DES. Interestingly, the level of GAP- 43 mRNA in the bed nucleus was reduced when males were treated with either TAM or CA and augmented when females were administered either DES or DHT. The results of these studies indicate that the effects of T on GAP-43 mRNA levels in the postnatal brain are modulated by estrogen- and androgen receptor- mediated events in a region-specific manner.

AB - The level of expression of the gene encoding GAP-43, a protein implicated in neurite outgrowth and motility, is sexually dimorphic in the postnatal brain and modulated by testosterone (T). To determine which metabolite of T modulates the expression of GAP-43 in the postnatal brain, the present study investigated the effect of estrogen and androgen receptor antagonists, tamoxifen (TAM) and cyproterone acetate (CA), and agonists, diethylstilbestrol (DES) and dihydrotestosterone (DHT). On postnatal day 1, male rats were injected sc daily with oil, TAM, or CA, whereas additional female pups were treated with oil, DES, or DHT. On postnatal day 6, brains were collected and 16-μm cryostat sections processed and hybridized with a 35S-labeled antisense riboprobe complementary to GAP-43 messenger RNA (mRNA). A comparison of hybridization signal in the cerebral cortex, bed nucleus of the stria terminalis, and medial preoptic nucleus demonstrated that the level of GAP-43 mRNA in males was significantly higher than in females. However, when male pups were injected with CA, a female-like level of GAP-43 mRNA was measured in the cerebral cortex. The low level of GAP-43 hybridization signal in the female cortex was markedly increased when females were treated with DHT. In contrast, the level of GAP-43 mRNA in the male medial preoptic nucleus was attenuated after treatment with TAM, whereas the level in the female was augmented with DES. Interestingly, the level of GAP- 43 mRNA in the bed nucleus was reduced when males were treated with either TAM or CA and augmented when females were administered either DES or DHT. The results of these studies indicate that the effects of T on GAP-43 mRNA levels in the postnatal brain are modulated by estrogen- and androgen receptor- mediated events in a region-specific manner.

UR - http://www.scopus.com/inward/record.url?scp=0028205844&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028205844&partnerID=8YFLogxK

U2 - 10.1210/en.134.3.1321

DO - 10.1210/en.134.3.1321

M3 - Article

C2 - 8119173

AN - SCOPUS:0028205844

VL - 134

SP - 1321

EP - 1328

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 3

ER -