Skip to main content
Top
Published in: BMC Endocrine Disorders 1/2018

Open Access 01-12-2018 | Research article

Effect of hypothyroidism on the hypothalamic–pituitary–ovarian axis and reproductive function of pregnant rats

Authors: Jianran Sun, Cancan Hui, Tongjia Xia, Min Xu, Datong Deng, Faming Pan, Youmin Wang

Published in: BMC Endocrine Disorders | Issue 1/2018

Login to get access

Abstract

Background

This study aimed to detect changes in hormone levels in the hypothalamic–pituitary–ovarian axis in Sprague-Dawley (SD) rats with hypothyroidism, and identify differences in the pregnancy and abortion rates of female adult rats. The potential role of gonadotropin releasing hormone (GnRH) as the link between the hypothalamic–pituitary–ovarian axis and reproductive function regulated by thyroid hormones was also investigated.

Methods

Female SD rats (n = 136) were causally classified into two groups: the normal-drinking-water group (n = 60) and the 0.05% propylthiouracil-drinking-water group (PTU 2 mg/kg/day, n = 76) to establish an adult rat model of hypothyroidism (6 weeks). Female and male rats at a ratio of 1:2 were used to establish a hypothyroidism pregnancy model. GnRH mRNA and GnRH receptor (GnRHR) expression in rats was detected using real time quantitative PCR(qRT-PCR) and immunohistochemistry, respectively.

Results

The abortion rate differed significantly between the hypothyroidism pregnancy group and the normal pregnancy group (P < 0.05). No significant differences were found in the distribution of the GnRHR among the five nuclei (hypothalamic arcuate nucleus, hypothalamic ventromedial nucleus, hypothalamic anterior nucleus, paraventricular nucleus of the hypothalamus, and ventral premammillary nucleus) of the hypothalamus and ovary (P > 0.05). Hypothyroidism had no significant effect on GnRH mRNA expression in the hypothalamic–pituitary–ovarian axis in the four groups (normal control group, normal pregnancy group, hypothyroidism pregnancy group, and hypothyroidism group) (P > 0.05).

Conclusions

Hypothyroidism had an adverse impact on pregnancy in rats and may affect the distribution of pituitary GnRHR, whereas it did not obviously affect the distribution of GnRHR in the nuclei of the hypothalamus and ovary. Hypothyroidism had no effect on GnRH mRNA expression.
Appendix
Available only for authorised users
Literature
1.
go back to reference Curto L, Trimarchi F. Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction. J Endocrinol Investig. 2016;39:1115–24.CrossRef Curto L, Trimarchi F. Hypopituitarism in the elderly: a narrative review on clinical management of hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-adrenal axes dysfunction. J Endocrinol Investig. 2016;39:1115–24.CrossRef
2.
go back to reference Flood DE, Fernandino JI, Langlois VS. Thyroid hormones in male reproductive development: evidence for direct crosstalk between the androgen and thyroid hormone axes. Gen Comp Endocrinol. 2013;192:2–14.CrossRefPubMed Flood DE, Fernandino JI, Langlois VS. Thyroid hormones in male reproductive development: evidence for direct crosstalk between the androgen and thyroid hormone axes. Gen Comp Endocrinol. 2013;192:2–14.CrossRefPubMed
3.
go back to reference Park CW, Choi MH, Yang KM, et al. Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment. Clinical and experimental reproductive medicine. 2016;43:169–73.CrossRefPubMedPubMedCentral Park CW, Choi MH, Yang KM, et al. Pregnancy rate in women with adenomyosis undergoing fresh or frozen embryo transfer cycles following gonadotropin-releasing hormone agonist treatment. Clinical and experimental reproductive medicine. 2016;43:169–73.CrossRefPubMedPubMedCentral
4.
go back to reference Cortes C, Langlois DC, VS Fernandino JI. Cross over of the hypothalamic pituitary-adrenal/interrenal,-thyroid, and-gonadal axes in testicular development. Front Endocrinol. 2014;5:139. Cortes C, Langlois DC, VS Fernandino JI. Cross over of the hypothalamic pituitary-adrenal/interrenal,-thyroid, and-gonadal axes in testicular development. Front Endocrinol. 2014;5:139.
5.
go back to reference Miccoli A, Olivotto I, De Felice A, et al. Characterization and transcriptional profiles of Engraulis encrasicolus' GnRH forms. Reproduction. 2016;152:727–39.CrossRefPubMed Miccoli A, Olivotto I, De Felice A, et al. Characterization and transcriptional profiles of Engraulis encrasicolus' GnRH forms. Reproduction. 2016;152:727–39.CrossRefPubMed
6.
go back to reference Duan JR, Fang DA, Zhang MY, et al. Changes of gonadotropin-releasing hormone receptor 2 during the anadromous spawning migration in Coilia nasus. BMC Dev Biol. 2016;16:42.CrossRefPubMedPubMedCentral Duan JR, Fang DA, Zhang MY, et al. Changes of gonadotropin-releasing hormone receptor 2 during the anadromous spawning migration in Coilia nasus. BMC Dev Biol. 2016;16:42.CrossRefPubMedPubMedCentral
7.
go back to reference Durand A, Bashamboo A, Mcelreavey K, et al. Familial early puberty: presentation and inheritance pattern in 139 families. BMC Endocr Disord. 2016;16:50.CrossRefPubMedPubMedCentral Durand A, Bashamboo A, Mcelreavey K, et al. Familial early puberty: presentation and inheritance pattern in 139 families. BMC Endocr Disord. 2016;16:50.CrossRefPubMedPubMedCentral
8.
go back to reference Jadhao AG, Pinelli CD. Aniello B, et al. gonadotropin-inhibitory hormone (GnRH) in the amphibian brain and its relationship with the gonadotropin releasing hormone (GnRH) system: an overview. Gen Comp Endocrinol. 2016;240:69–76.CrossRefPubMed Jadhao AG, Pinelli CD. Aniello B, et al. gonadotropin-inhibitory hormone (GnRH) in the amphibian brain and its relationship with the gonadotropin releasing hormone (GnRH) system: an overview. Gen Comp Endocrinol. 2016;240:69–76.CrossRefPubMed
9.
go back to reference Ciechanowska M, Lapot M, Mateusiak K, et al. The central effect of beta-endorphin and naloxone on the biosynthesis of GnRH and GnRH receptor (GnRHR) in the hypothalamic-pituitary unit of follicular-phase ewes. Reprod Domest Anim. 2016;51:555–61.CrossRefPubMed Ciechanowska M, Lapot M, Mateusiak K, et al. The central effect of beta-endorphin and naloxone on the biosynthesis of GnRH and GnRH receptor (GnRHR) in the hypothalamic-pituitary unit of follicular-phase ewes. Reprod Domest Anim. 2016;51:555–61.CrossRefPubMed
10.
go back to reference Cimino I, Casoni F, Liu X, et al. Novel role for anti-Mullerian hormone in the regulation of GnRH neuron excitability and hormone secretion. Nat Commun. 2016;7:10055.CrossRefPubMedPubMedCentral Cimino I, Casoni F, Liu X, et al. Novel role for anti-Mullerian hormone in the regulation of GnRH neuron excitability and hormone secretion. Nat Commun. 2016;7:10055.CrossRefPubMedPubMedCentral
12.
go back to reference Mann DR, Plant TM. The role and potential sites of action of thyroid hormone in timing the onset of puberty in male primates. Brain Res. 2010;1364:175–85.CrossRefPubMedPubMedCentral Mann DR, Plant TM. The role and potential sites of action of thyroid hormone in timing the onset of puberty in male primates. Brain Res. 2010;1364:175–85.CrossRefPubMedPubMedCentral
13.
go back to reference Shaffer JP. Controlling the false discovery rate with constraints: the Newman-Keuls test revisited. Biom J. 2007;49(1):136–43.CrossRefPubMed Shaffer JP. Controlling the false discovery rate with constraints: the Newman-Keuls test revisited. Biom J. 2007;49(1):136–43.CrossRefPubMed
14.
go back to reference De Muth JE. Basic Statistics and Pharmaceutical Statistical Applications. 2nd ed. Boca Raton, FL: Chapman and Hall/CRC; 2006. p. 229–59. De Muth JE. Basic Statistics and Pharmaceutical Statistical Applications. 2nd ed. Boca Raton, FL: Chapman and Hall/CRC; 2006. p. 229–59.
15.
go back to reference Yang J, Zhou X, Zhang X, et al. Analysis of the correlation between lipotoxicity and pituitary-thyroid axis hormone levels in men and male rats. Oncotarget. 2016;7:39332–44.PubMedPubMedCentral Yang J, Zhou X, Zhang X, et al. Analysis of the correlation between lipotoxicity and pituitary-thyroid axis hormone levels in men and male rats. Oncotarget. 2016;7:39332–44.PubMedPubMedCentral
16.
go back to reference Coelho Neto MAMWP, Melo AS, et al. Subclinical hypothyroidism and intracytoplasmic sperm injection outcomes. Rev Bras Ginecol Obstet. 2016;38:552–8.CrossRefPubMed Coelho Neto MAMWP, Melo AS, et al. Subclinical hypothyroidism and intracytoplasmic sperm injection outcomes. Rev Bras Ginecol Obstet. 2016;38:552–8.CrossRefPubMed
17.
go back to reference Andersen SL, Olsen J. Early pregnancy thyroid function test abnormalities in biobanksera from women clinically diagnosed before or after the pregnancy. Thyroid. 2017;27:451–9.CrossRefPubMed Andersen SL, Olsen J. Early pregnancy thyroid function test abnormalities in biobanksera from women clinically diagnosed before or after the pregnancy. Thyroid. 2017;27:451–9.CrossRefPubMed
18.
go back to reference Ajmani SN, Aggarwal D, Bhatia P, et al. Prevalence of overt and subclinical thyroid dysfunction among pregnant women and its effect on maternal and fetal outcome. J Obstet Gynaecol India. 2014;64:105–10.CrossRefPubMed Ajmani SN, Aggarwal D, Bhatia P, et al. Prevalence of overt and subclinical thyroid dysfunction among pregnant women and its effect on maternal and fetal outcome. J Obstet Gynaecol India. 2014;64:105–10.CrossRefPubMed
19.
go back to reference Casey B, De Veciana M. Thyroid screening in pregnancy. American journal of obstetrics and gynecology. 2014;211:351–3. e1CrossRefPubMed Casey B, De Veciana M. Thyroid screening in pregnancy. American journal of obstetrics and gynecology. 2014;211:351–3. e1CrossRefPubMed
20.
go back to reference Maraka S, Ospina NM, O'keeffe DT, et al. Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis. Thyroid: official journal of the American Thyroid Association. 2016;26:580–90.CrossRef Maraka S, Ospina NM, O'keeffe DT, et al. Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis. Thyroid: official journal of the American Thyroid Association. 2016;26:580–90.CrossRef
21.
go back to reference No authors listed. Pulsatile control of reproduction. Lancet. 1984;2:382–23. No authors listed. Pulsatile control of reproduction. Lancet. 1984;2:382–23.
22.
go back to reference Vastagh C, Rodolosse A, Solymosi N, et al. Altered expression of genes encoding neurotransmitter receptors in GnRH neurons of proestrous mice. Front Cell Neurosci. 2016;10:230.CrossRefPubMedPubMedCentral Vastagh C, Rodolosse A, Solymosi N, et al. Altered expression of genes encoding neurotransmitter receptors in GnRH neurons of proestrous mice. Front Cell Neurosci. 2016;10:230.CrossRefPubMedPubMedCentral
23.
go back to reference Kim SM, Lee M, Lee SY, et al. Discovery of an orally bioavailable gonadotropin-releasing hormone receptor antagonist. J Med Chem. 2016;59:9150–72.CrossRefPubMed Kim SM, Lee M, Lee SY, et al. Discovery of an orally bioavailable gonadotropin-releasing hormone receptor antagonist. J Med Chem. 2016;59:9150–72.CrossRefPubMed
24.
go back to reference Piet R, Dunckley H, Lee K, et al. Vasoactive intestinal peptide excites GnRH neurons in male and female mice. Endocrinology. 2016;157:3621–30.CrossRefPubMed Piet R, Dunckley H, Lee K, et al. Vasoactive intestinal peptide excites GnRH neurons in male and female mice. Endocrinology. 2016;157:3621–30.CrossRefPubMed
25.
go back to reference Larco DO, Semsarzadeh NN, Cho-Clark M, et al. The novel actions of the metabolite GnRH-(1-5) are mediated by a G protein-coupled receptor. Front Endocrinol. 2013;4:83.CrossRef Larco DO, Semsarzadeh NN, Cho-Clark M, et al. The novel actions of the metabolite GnRH-(1-5) are mediated by a G protein-coupled receptor. Front Endocrinol. 2013;4:83.CrossRef
26.
go back to reference Bianco SD, Kaiser UB. Molecular biology of the kisspeptin receptor: signaling, function, and mutations. Adv Exp Med Biol. 2013;784:133–58.CrossRefPubMed Bianco SD, Kaiser UB. Molecular biology of the kisspeptin receptor: signaling, function, and mutations. Adv Exp Med Biol. 2013;784:133–58.CrossRefPubMed
27.
go back to reference Ramakrishnappa N, Rajamahendran R, Lin YM, et al. GnRH in non-hypothalamic reproductive tissues. Anim Reprod Sci. 2005;88:95–113.CrossRefPubMed Ramakrishnappa N, Rajamahendran R, Lin YM, et al. GnRH in non-hypothalamic reproductive tissues. Anim Reprod Sci. 2005;88:95–113.CrossRefPubMed
28.
go back to reference Lehman MN, Goodman RL, Karsch FJ, et al. The GnRH system of seasonal breeders: anatomy and plasticity. Brain Res Bull. 1997;44:445–57.CrossRefPubMed Lehman MN, Goodman RL, Karsch FJ, et al. The GnRH system of seasonal breeders: anatomy and plasticity. Brain Res Bull. 1997;44:445–57.CrossRefPubMed
29.
go back to reference Singh BK, Yen PM. A clinician's guide to understanding resistance to thyroid hormone due to receptor mutations in the TRalpha and TRbeta isoforms. Clinical diabetes and endocrinology. 2017;3:8.CrossRefPubMedPubMedCentral Singh BK, Yen PM. A clinician's guide to understanding resistance to thyroid hormone due to receptor mutations in the TRalpha and TRbeta isoforms. Clinical diabetes and endocrinology. 2017;3:8.CrossRefPubMedPubMedCentral
30.
go back to reference Populo H, Nunes B, Sampaio C, et al. Inhibitory effects of antagonists of growth hormone-releasing hormone (GHRH) in thyroid Cancer. Hormones & cancer. 2017;8(5–6):314–24.CrossRef Populo H, Nunes B, Sampaio C, et al. Inhibitory effects of antagonists of growth hormone-releasing hormone (GHRH) in thyroid Cancer. Hormones & cancer. 2017;8(5–6):314–24.CrossRef
31.
go back to reference Yoshimura T. Thyroid hormone and seasonal regulation of reproduction. Front Neuroendocrinol. 2013;34(3):157–66.CrossRefPubMed Yoshimura T. Thyroid hormone and seasonal regulation of reproduction. Front Neuroendocrinol. 2013;34(3):157–66.CrossRefPubMed
32.
go back to reference Liu J, Guo M, Hu X, et al. Effects of Thyroid Dysfunction on Reproductive Hormones in Female Rats. Chin J Physiol. 2018;61. [Epub ahead of print]. Liu J, Guo M, Hu X, et al. Effects of Thyroid Dysfunction on Reproductive Hormones in Female Rats. Chin J Physiol. 2018;61. [Epub ahead of print].
33.
go back to reference Ikegami K, Yoshimura T. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction. Gen Comp Endocrinol. 2016;227:64–8.CrossRefPubMed Ikegami K, Yoshimura T. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction. Gen Comp Endocrinol. 2016;227:64–8.CrossRefPubMed
34.
go back to reference Nakayama T, Yoshimura T. Seasonal rhythms: the role of thyrotropin and thyroid hormones. Thyroid: official journal of the American Thyroid Association. 2018;28(1):4–10.CrossRef Nakayama T, Yoshimura T. Seasonal rhythms: the role of thyrotropin and thyroid hormones. Thyroid: official journal of the American Thyroid Association. 2018;28(1):4–10.CrossRef
Metadata
Title
Effect of hypothyroidism on the hypothalamic–pituitary–ovarian axis and reproductive function of pregnant rats
Authors
Jianran Sun
Cancan Hui
Tongjia Xia
Min Xu
Datong Deng
Faming Pan
Youmin Wang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Endocrine Disorders / Issue 1/2018
Electronic ISSN: 1472-6823
DOI
https://doi.org/10.1186/s12902-018-0258-y

Other articles of this Issue 1/2018

BMC Endocrine Disorders 1/2018 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.