Excess testosterone exposure alters hypothalamic-pituitary-Testicular axis dynamics and gene expression in sheep fetuses

Charles E. Roselli, Rebecka Amodei, Kyle P. Gribbin, Keely Corder, Fred Stormshak, Charles T. Estill

Research output: Research - peer-reviewArticle

Abstract

Prenatal exposure to excess androgen may result in impaired adult fertility in a variety of mammalian species. However, little is known about what feedback mechanisms regulate gonadotropin secretion during early gestation and how they respond to excess T exposure. The objective of this study was to determine the effect of exogenous exposure to T on key genes that regulate gonadotropin and GnRH secretion in fetal male lambs as compared with female cohorts. We found that biweekly maternal testosterone propionate (100 mg) treatment administered from day 30 to day 58 of gestation acutely decreased (P < .05) serum LH concentrations and reduced the expression of gonadotropin subunitmRNAin both sexesandthe levels ofGnRHreceptormRNAin males. These results are consistent with enhanced negative feedback at the level of the pituitary and were accompanied by reducedmRNAlevels for testicular steroidogenic enzymes, suggesting that Leydig cell function was also suppressed. The expression of kisspeptin 1 mRNA, a key regulator of GnRH neurons, was significantly greater (P<.01) in control females than in males and reduced (P<.001) in females by T exposure, indicating that hypothalamic regulation of gonadotropin secretion was also affected by androgen exposure. Although endocrine homeostasis was reestablished 2 weeks after maternal testosterone propionate treatment ceased, additional differences in the gene expression of GnRH, estrogen receptor β and kisspeptin receptor (G protein coupled receptor 54) emerged between the treatment cohorts. These changes suggest the normal trajectory of hypothalamic-pituitary axis development was disrupted, which may, in turn, contribute to negative effects on fertility later in life.

LanguageEnglish (US)
Pages4234-4245
Number of pages12
JournalEndocrinology
Volume157
Issue number11
DOIs
StatePublished - Nov 1 2016

Fingerprint

Gonadotropins
Testosterone
Sheep
Fetus
Gene Expression
Kisspeptins
Testosterone Propionate
Gonadotropin-Releasing Hormone
Androgens
Fertility
Mothers
Pregnancy
LHRH Receptors
Estrogen Receptor beta
Leydig Cells
G-Protein-Coupled Receptors
Homeostasis
Neurons
Messenger RNA
Enzymes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Excess testosterone exposure alters hypothalamic-pituitary-Testicular axis dynamics and gene expression in sheep fetuses. / Roselli, Charles E.; Amodei, Rebecka; Gribbin, Kyle P.; Corder, Keely; Stormshak, Fred; Estill, Charles T.

In: Endocrinology, Vol. 157, No. 11, 01.11.2016, p. 4234-4245.

Research output: Research - peer-reviewArticle

Roselli, CE, Amodei, R, Gribbin, KP, Corder, K, Stormshak, F & Estill, CT 2016, 'Excess testosterone exposure alters hypothalamic-pituitary-Testicular axis dynamics and gene expression in sheep fetuses' Endocrinology, vol 157, no. 11, pp. 4234-4245. DOI: 10.1210/en.2016-1411
Roselli CE, Amodei R, Gribbin KP, Corder K, Stormshak F, Estill CT. Excess testosterone exposure alters hypothalamic-pituitary-Testicular axis dynamics and gene expression in sheep fetuses. Endocrinology. 2016 Nov 1;157(11):4234-4245. Available from, DOI: 10.1210/en.2016-1411
Roselli, Charles E. ; Amodei, Rebecka ; Gribbin, Kyle P. ; Corder, Keely ; Stormshak, Fred ; Estill, Charles T./ Excess testosterone exposure alters hypothalamic-pituitary-Testicular axis dynamics and gene expression in sheep fetuses. In: Endocrinology. 2016 ; Vol. 157, No. 11. pp. 4234-4245
@article{45325610f29447eb90dd8be9e08913bd,
title = "Excess testosterone exposure alters hypothalamic-pituitary-Testicular axis dynamics and gene expression in sheep fetuses",
abstract = "Prenatal exposure to excess androgen may result in impaired adult fertility in a variety of mammalian species. However, little is known about what feedback mechanisms regulate gonadotropin secretion during early gestation and how they respond to excess T exposure. The objective of this study was to determine the effect of exogenous exposure to T on key genes that regulate gonadotropin and GnRH secretion in fetal male lambs as compared with female cohorts. We found that biweekly maternal testosterone propionate (100 mg) treatment administered from day 30 to day 58 of gestation acutely decreased (P < .05) serum LH concentrations and reduced the expression of gonadotropin subunitmRNAin both sexesandthe levels ofGnRHreceptormRNAin males. These results are consistent with enhanced negative feedback at the level of the pituitary and were accompanied by reducedmRNAlevels for testicular steroidogenic enzymes, suggesting that Leydig cell function was also suppressed. The expression of kisspeptin 1 mRNA, a key regulator of GnRH neurons, was significantly greater (P<.01) in control females than in males and reduced (P<.001) in females by T exposure, indicating that hypothalamic regulation of gonadotropin secretion was also affected by androgen exposure. Although endocrine homeostasis was reestablished 2 weeks after maternal testosterone propionate treatment ceased, additional differences in the gene expression of GnRH, estrogen receptor β and kisspeptin receptor (G protein coupled receptor 54) emerged between the treatment cohorts. These changes suggest the normal trajectory of hypothalamic-pituitary axis development was disrupted, which may, in turn, contribute to negative effects on fertility later in life.",
author = "Roselli, {Charles E.} and Rebecka Amodei and Gribbin, {Kyle P.} and Keely Corder and Fred Stormshak and Estill, {Charles T.}",
year = "2016",
month = "11",
doi = "10.1210/en.2016-1411",
volume = "157",
pages = "4234--4245",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "11",

}

TY - JOUR

T1 - Excess testosterone exposure alters hypothalamic-pituitary-Testicular axis dynamics and gene expression in sheep fetuses

AU - Roselli,Charles E.

AU - Amodei,Rebecka

AU - Gribbin,Kyle P.

AU - Corder,Keely

AU - Stormshak,Fred

AU - Estill,Charles T.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Prenatal exposure to excess androgen may result in impaired adult fertility in a variety of mammalian species. However, little is known about what feedback mechanisms regulate gonadotropin secretion during early gestation and how they respond to excess T exposure. The objective of this study was to determine the effect of exogenous exposure to T on key genes that regulate gonadotropin and GnRH secretion in fetal male lambs as compared with female cohorts. We found that biweekly maternal testosterone propionate (100 mg) treatment administered from day 30 to day 58 of gestation acutely decreased (P < .05) serum LH concentrations and reduced the expression of gonadotropin subunitmRNAin both sexesandthe levels ofGnRHreceptormRNAin males. These results are consistent with enhanced negative feedback at the level of the pituitary and were accompanied by reducedmRNAlevels for testicular steroidogenic enzymes, suggesting that Leydig cell function was also suppressed. The expression of kisspeptin 1 mRNA, a key regulator of GnRH neurons, was significantly greater (P<.01) in control females than in males and reduced (P<.001) in females by T exposure, indicating that hypothalamic regulation of gonadotropin secretion was also affected by androgen exposure. Although endocrine homeostasis was reestablished 2 weeks after maternal testosterone propionate treatment ceased, additional differences in the gene expression of GnRH, estrogen receptor β and kisspeptin receptor (G protein coupled receptor 54) emerged between the treatment cohorts. These changes suggest the normal trajectory of hypothalamic-pituitary axis development was disrupted, which may, in turn, contribute to negative effects on fertility later in life.

AB - Prenatal exposure to excess androgen may result in impaired adult fertility in a variety of mammalian species. However, little is known about what feedback mechanisms regulate gonadotropin secretion during early gestation and how they respond to excess T exposure. The objective of this study was to determine the effect of exogenous exposure to T on key genes that regulate gonadotropin and GnRH secretion in fetal male lambs as compared with female cohorts. We found that biweekly maternal testosterone propionate (100 mg) treatment administered from day 30 to day 58 of gestation acutely decreased (P < .05) serum LH concentrations and reduced the expression of gonadotropin subunitmRNAin both sexesandthe levels ofGnRHreceptormRNAin males. These results are consistent with enhanced negative feedback at the level of the pituitary and were accompanied by reducedmRNAlevels for testicular steroidogenic enzymes, suggesting that Leydig cell function was also suppressed. The expression of kisspeptin 1 mRNA, a key regulator of GnRH neurons, was significantly greater (P<.01) in control females than in males and reduced (P<.001) in females by T exposure, indicating that hypothalamic regulation of gonadotropin secretion was also affected by androgen exposure. Although endocrine homeostasis was reestablished 2 weeks after maternal testosterone propionate treatment ceased, additional differences in the gene expression of GnRH, estrogen receptor β and kisspeptin receptor (G protein coupled receptor 54) emerged between the treatment cohorts. These changes suggest the normal trajectory of hypothalamic-pituitary axis development was disrupted, which may, in turn, contribute to negative effects on fertility later in life.

UR - http://www.scopus.com/inward/record.url?scp=84994310439&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84994310439&partnerID=8YFLogxK

U2 - 10.1210/en.2016-1411

DO - 10.1210/en.2016-1411

M3 - Article

VL - 157

SP - 4234

EP - 4245

JO - Endocrinology

T2 - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 11

ER -