Involvement of gonadotropins in the induction of hypertrophy-hyperplasia in the interstitial tissues of ovaries in neonatally diethylstilbestrol-treated mice

Hanako Kakuta; Masami Tanaka; Pierre Chambon; Hajime Watanabe; Taisen Iguchi; Tomomi Sato

doi:10.1016/j.reprotox.2011.10.013

Involvement of gonadotropins in the induction of hypertrophy-hyperplasia in the interstitial tissues of ovaries in neonatally diethylstilbestrol-treated mice

Reprod Toxicol. 2012 Jan;33(1):35-44. doi: 10.1016/j.reprotox.2011.10.013. Epub 2011 Nov 12.

Authors

Hanako Kakuta¹, Masami Tanaka, Pierre Chambon, Hajime Watanabe, Taisen Iguchi, Tomomi Sato

Affiliation

¹ International Graduate School of Arts and Sciences, Yokohama City University, Yokohama 236-0027, Japan.

PMID: 22100434
DOI: 10.1016/j.reprotox.2011.10.013

Abstract

Neonatally diethylstilbestrol (DES) treatment causes hypertrophy-hyperplasia in the interstitial tissue of mouse ovaries. To understand the induction mechanism of the hypertrophy, mRNA expression involved in steroidogenesis in the ovary of neonatally DES-treated mice was examined. The expression of StAR and Cyp11a1 was significantly reduced while Cyp19 and Sf-1 were stimulated in the ovary of neonatally DES-treated 3-month-old mice. Expression of those genes was not different between DES- and oil-treated mice after the gonadotropins treatment. Lhb in the pituitary of 3-month-old neonatally DES-treated mice was significantly decreased. Finally, ovaries from DES-treated mice transplanted to neonatally oil-treated hosts had developing follicles at several stages and corpora lutea, whereas grafted ovaries from neonatally oil-treated mice in 3-month-old neonatally DES-treated hosts showed lipid accumulation in the interstitial tissue. Thus, hypertrophy and accumulation of lipid droplets in interstitial cells of neonatally DES-treated mice is caused by impaired steroidogenesis due to the alterations of gonadotropins levels.

MeSH terms

Age Factors
Animals
Animals, Newborn
Aromatase / genetics
Cytochrome P-450 CYP1A1 / genetics
Diethylstilbestrol / administration & dosage
Diethylstilbestrol / toxicity*
Estradiol / blood
Estrogen Receptor alpha / deficiency
Estrogen Receptor alpha / drug effects
Estrogen Receptor alpha / genetics
Estrogen Receptor beta / drug effects
Estrogen Receptor beta / genetics
Estrogen Receptor beta / metabolism
Estrogens, Non-Steroidal / administration & dosage
Estrogens, Non-Steroidal / toxicity*
Female
Follicle Stimulating Hormone, beta Subunit / metabolism
Gene Expression Regulation / drug effects
Glycoprotein Hormones, alpha Subunit / metabolism
Gonadotropins / genetics
Gonadotropins / metabolism*
Hyperplasia
Hypertrophy
Lipid Metabolism / drug effects
Luteinizing Hormone, beta Subunit / metabolism
Mice
Mice, 129 Strain
Mice, Inbred C57BL
Mice, Knockout
Ovariectomy
Ovary / drug effects*
Ovary / metabolism
Ovary / pathology
Ovary / transplantation
Phosphoproteins / genetics
Pituitary Gland, Anterior / drug effects*
Pituitary Gland, Anterior / metabolism
RNA, Messenger / metabolism
Steroidogenic Factor 1 / genetics
Theca Cells / drug effects*
Theca Cells / metabolism
Theca Cells / pathology

Substances

Estrogen Receptor alpha
Estrogen Receptor beta
Estrogens, Non-Steroidal
Follicle Stimulating Hormone, beta Subunit
Glycoprotein Hormones, alpha Subunit
Gonadotropins
Luteinizing Hormone, beta Subunit
Phosphoproteins
RNA, Messenger
Steroidogenic Factor 1
steroidogenic acute regulatory protein
Estradiol
Diethylstilbestrol
Aromatase
Cytochrome P-450 CYP1A1