Skip to main content
SpringerLink
Log in

Regulation of glucose transport by thyroid hormone in rat ovary

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Thyroid hormone (TH) plays an important role in regulating ovarian development. However, the mechanism involved remains unclear. Evidence suggests that glucose is essential for ovarian development, and its uptake is mediated by several glucose transporter proteins (Glut). We have investigated the effects of TH on Glut in rat ovary. Immature rats were treated with 6-propyl-2-thiouracil or L-thyroxine to induce hypothyroidism (hypo) or hyperthyroidism (hyper), respectively. Ovarian weights significantly decreased in both treated groups compared with the control group, although the body weights were not markedly altered. Glut1 expression significantly decreased without further changes being detected in the other Glut isforms in the hypo group and was accompanied by minimal change in mRNA content. The expression of Glut1 decreased in the hyper group. In contrast, L-thyroxine significantly increased Glut4 mRNA level and protein content but had little effect on Glut2 and Glut3 expression. Serum glucose concentrations in the hyper group were dramatically reduced compared with those in the control group. However, the serum glucose levels in the hypo group were not significantly changed. In addition, equine chorionic gonadotropin (eCG) increased ovarian weights in both the hypo and hyper groups compared with those in the rats without eCG injection. Glut2–4 protein content was significantly increased by eCG in hyper rats. Only the Glut4 mRNA content was significantly increased by eCG in the hyper group. Although the mRNA levels were not significantly changed by eCG in the hypo group, the protein level of Glut4 was markedly up-regulated. Serum glucose levels were not significantly altered by eCG in the two groups. Thus, dysfunction of the thyroid gland changes Glut expression in rat ovary and ovarian growth, both of which are also regulated by gonadotropin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

TH, T3, or T4 :

Thyroid hormone

Hypo:

Hypothyroidism

Hyper:

Hyperthyroidism

Glut:

Glucose transport

eCG:

Equine chorionic gonadotropin

GnRH:

Gonadotropin-releasing hormone

FSH:

Follicle-stimulating hormone

LH:

Luteinizing hormone

IU:

International units

PTU:

6-Propyl-2-thiouracil

PBS:

Phosphate-buffered saline

RIA:

Radio-immunoassay

TSH:

Thyroid-stimulating hormone

References

  • Akande EO, Hockaday TD (1975) Plasma concentration of gonadotrophins, oestrogens and progesterone in thyrotoxic women. Br J Obstet Gynaecol 82:541–551

    Article  CAS  PubMed  Google Scholar 

  • Alexanderson C, Stener-Victorin E, Kullberg J, Nilsson S, Levin M, Cajander S, Lonn L, Lonn M, Holmang A (2010) A single early postnatal estradiol injection affects morphology and gene expression of the ovary and parametrial adipose tissue in adult female rats. J Steroid Biochem Mol Biol 122:82–90

    Article  CAS  PubMed  Google Scholar 

  • Ayala C, Valdez SR, Morero ML, Soaje M, Carreno NB, Sanchez MS, Bittencourt JC, Jahn GA, Celis ME (2011) Hypo- and hyperthyroidism affect NEI concentration in discrete brain areas of adult male rats. Peptides 32:1249–1254

    Article  CAS  PubMed  Google Scholar 

  • Baird D (2006) Role of FSH and LH in follicle development. J Gynecol Obstet Biol Reprod (Paris) 35:2S24–2S29

    Article  CAS  Google Scholar 

  • Bartlewski PM, Vanderpol J, Beard AP, Cook SJ, Rawlings NC (2000) Ovarian antral follicular dynamics and their associations with peripheral concentrations of gonadotropins and ovarian steroids in anoestrous Finnish Landrace ewes. Anim Reprod Sci 58:273–291

    Article  CAS  PubMed  Google Scholar 

  • Brunetto EL, Teixeira Sda S, Giannocco G, Machado UF, Nunes MT (2012) T3 rapidly increases SLC2A4 gene expression and GLUT4 trafficking to the plasma membrane in skeletal muscle of rat and improves glucose homeostasis. Thyroid 22:70–79

    Article  CAS  PubMed  Google Scholar 

  • Cettour-Rose P, Theander-Carrillo C, Asensio C, Klein M, Visser TJ, Burger AG, Meier CA, Rohner-Jeanrenaud F (2005) Hypothyroidism in rats decreases peripheral glucose utilisation, a defect partially corrected by central leptin infusion. Diabetologia 48:624–633

    Article  CAS  PubMed  Google Scholar 

  • Darras VM, Van Herck SL, Geysens S, Reyns GE (2009) Involvement of thyroid hormones in chicken embryonic brain development. Gen Comp Endocrinol 163:58–62

    Article  CAS  PubMed  Google Scholar 

  • Deng D, Yan N (2016) GLUT, SGLT, and SWEET: structural and mechanistic investigations of the glucose transporters. Protein Sci 25:546–558

    Article  CAS  PubMed  Google Scholar 

  • Dimitriadis G, Maratou E, Alevizaki M, Boutati E, Psara K, Papasteriades C, Raptis SA (2005) Thyroid hormone excess increases basal and insulin-stimulated recruitment of GLUT3 glucose transporters on cell surface. Horm Metab Res 37:15–20

    Article  CAS  PubMed  Google Scholar 

  • Dittrich R, Beckmann MW, Oppelt PG, Hoffmann I, Lotz L, Kuwert T, Mueller A (2011) Thyroid hormone receptors and reproduction. J Reprod Immunol 90:58–66

    Article  CAS  PubMed  Google Scholar 

  • Fedail JS, Zheng K, Wei Q, Kong L, Shi F (2014) Roles of thyroid hormones in follicular development in the ovary of neonatal and immature rats. Endocrine 46:594–604

    Article  CAS  PubMed  Google Scholar 

  • Garcia-Flores M, Blazquez E, Zueco JA (2001) Effects of triiodothyronine and bovine growth hormone on glucose transporter isoform-2 (GLUT-2) and glucokinase (GK) gene expression in pancreatic islets of fetal and adult rats. Pflugers Arch 442:662–667

    Article  CAS  PubMed  Google Scholar 

  • Hapon MB, Varas SM, Jahn GA, Gimenez MS (2005) Effects of hypothyroidism on mammary and liver lipid metabolism in virgin and late-pregnant rats. J Lipid Res 46:1320–1330

    Article  CAS  PubMed  Google Scholar 

  • Hirshfield AN (1997) Overview of ovarian follicular development: considerations for the toxicologist. Environ Mol Mutagen 29:10–15

    Article  CAS  PubMed  Google Scholar 

  • Jiang JY, Miyoshi K, Umezu M, Sato E (1999) Superovulation of immature hypothyroid rdw rats by thyroxine therapy and the development of eggs after in vitro fertilization. J Reprod Fertil 116:19–24

    Article  CAS  PubMed  Google Scholar 

  • Jiang JY, Umezu M, Sato E (2000) Improvement of follicular development rather than gonadotrophin secretion by thyroxine treatment in infertile immature hypothyroid rdw rats. J Reprod Fertil 119:193–199

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi N, Orisaka M, Cao M, Kotsuji F, Leader A, Sakuragi N, Tsang BK (2009) Growth differentiation factor-9 mediates follicle-stimulating hormone-thyroid hormone interaction in the regulation of rat preantral follicular development. Endocrinology 150:5566–5574

    Article  CAS  PubMed  Google Scholar 

  • Kodaman PH, Behrman HR (1999) Hormone-regulated and glucose-sensitive transport of dehydroascorbic acid in immature rat granulosa cells. Endocrinology 140:3659–3665

    CAS  PubMed  Google Scholar 

  • Koibuchi N (2008) The role of thyroid hormone on cerebellar development. Cerebellum 7:530–533

    Article  CAS  PubMed  Google Scholar 

  • Kol S, Ben-Shlomo I, Ruutiainen K, Ando M, Davies-Hill TM, Rohan RM, Simpson IA, Adashi EY (1997) The midcycle increase in ovarian glucose uptake is associated with enhanced expression of glucose transporter 3. Possible role for interleukin-1, a putative intermediary in the ovulatory process. J Clin Invest 99:2274–2283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kong L, Wei Q, Fedail JS, Shi F, Nagaoka K, Watanabe G (2015) Effects of thyroid hormones on the antioxidative status in the uterus of young adult rats. J Reprod Development 61:219–227

    Article  Google Scholar 

  • Kuruvilla AK, Perez C, Ismail-Beigi F, Loeb JN (1991) Regulation of glucose transport in Clone 9 cells by thyroid hormone. Biochim Biophys Acta 1094:300–308

    Article  CAS  PubMed  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25:402–408

    Article  CAS  PubMed  Google Scholar 

  • Matthaei S, Trost B, Hamann A, Kausch C, Benecke H, Greten H, Hoppner W, Klein HH (1995) Effect of in vivo thyroid hormone status on insulin signalling and GLUT1 and GLUT4 glucose transport systems in rat adipocytes. J Endocrinol 144:347–357

    Article  CAS  PubMed  Google Scholar 

  • Mooradian AD, Chehade JM, Kim J (1999) Age-related changes in thyroid hormone effects on glucose transporter isoforms of rat heart. Life Sci 65:981–989

    Article  CAS  PubMed  Google Scholar 

  • Nishimoto H, Matsutani R, Yamamoto S, Takahashi T, Hayashi KG, Miyamoto A, Hamano S, Tetsuka M (2006) Gene expression of glucose transporter (GLUT) 1, 3 and 4 in bovine follicle and corpus luteum. J Endocrinol 188:111–119

    Article  CAS  PubMed  Google Scholar 

  • Portman MA (2008) Thyroid hormone regulation of perinatal cardiovascular function. Semin Perinatol 32:419–422

    Article  PubMed  Google Scholar 

  • Ramachandran V, Saravanan R (2015) Glucose uptake through translocation and activation of GLUT4 in PI3K/Akt signaling pathway by asiatic acid in diabetic rats. Hum Exp Toxicol 34:884–893

    Article  CAS  PubMed  Google Scholar 

  • Richards JS, Sharma SC, Falender AE, Lo YH (2002) Expression of FKHR, FKHRL1, and AFX genes in the rodent ovary: evidence for regulation by IGF-I, estrogen, and the gonadotropins. Mol Endocrinol 16:580–599

    Article  CAS  PubMed  Google Scholar 

  • Romero R, Casanova B, Pulido N, Suarez AI, Rodriguez E, Rovira A (2000) Stimulation of glucose transport by thyroid hormone in 3T3-L1 adipocytes: increased abundance of GLUT1 and GLUT4 glucose transporter proteins. J Endocrinol 164:187–195

    Article  CAS  PubMed  Google Scholar 

  • Saran S, Gupta BS, Philip R, Singh KS, Bende SA, Agroiya P, Agrawal P (2016) Effect of hypothyroidism on female reproductive hormones. Indian J Endocrinol Metab 20:108–113

    Article  PubMed  PubMed Central  Google Scholar 

  • Sharawy MH, El-Awady MS, Megahed N, Gameil NM (2016) Attenuation of insulin resistance in rats by agmatine: role of SREBP-1c, mTOR and GLUT-2. Naunyn Schmiedebergs Arch Pharmacol 389:45–56

    Article  CAS  PubMed  Google Scholar 

  • Shetty M, Kuruvilla AK, Ismail-Beigi F, Loeb JN (1996) Stimulation of glucose transport in Clone 9 cells by insulin and thyroid hormone: role of GLUT-1 activation. Biochim Biophys Acta 1314:140–146

    Article  PubMed  Google Scholar 

  • Shimizu Y, Shimazu T (2002) Thyroid hormone augments GLUT4 expression and insulin-sensitive glucose transport system in differentiating rat brown adipocytes in culture. J Vet Med Sci 64:677–681

    Article  CAS  PubMed  Google Scholar 

  • Silvestri E, Burrone L, Lange P de, Lombardi A, Farina P, Chambery A, Parente A, Lanni A, Goglia F, Moreno M (2007) Thyroid-state influence on protein-expression profile of rat skeletal muscle. J Proteome Res 6:3187–3196

  • Sugden MC, Liu YL, Holness MJ (1990) Glucose utilization by skeletal muscles in vivo in experimental hyperthyroidism in the rat. Biochem J 271:421–425

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teixeira SS, Tamrakar AK, Goulart-Silva F, Serrano-Nascimento C, Klip A, Nunes MT (2012) Triiodothyronine acutely stimulates glucose transport into L6 muscle cells without increasing surface GLUT4, GLUT1, or GLUT3. Thyroid 22:747–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ueda-Wakagi M, Mukai R, Fuse N, Mizushina Y, Ashida H (2015) 3-O-Acyl-epicatechins increase glucose uptake activity and GLUT4 translocation through activation of PI3K signaling in skeletal muscle cells. Int J Mol Sci 16:16288–16299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wei J, Shimazu J, Makinistoglu MP, Maurizi A, Kajimura D, Zong H, Takarada T, Iezaki T, Pessin JE, Hinoi E, Karsenty G (2015) Glucose uptake and Runx2 synergize to orchestrate osteoblast differentiation and bone formation. Cell 161:1576–1591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weinstein SP, Haber RS (1993) Glucose transport stimulation by thyroid hormone in ARL 15 cells: partial role of increased GLUT1 glucose transporter gene transcription. Thyroid 3:135–142

    Article  CAS  PubMed  Google Scholar 

  • Weinstein SP, Watts J, Haber RS (1991) Thyroid hormone increases muscle/fat glucose transporter gene expression in rat skeletal muscle. Endocrinology 129:455–464

    Article  CAS  PubMed  Google Scholar 

  • Williams SA, Blache D, Martin GB, Foot R, Blackberry MA, Scaramuzzi RJ (2001) Effect of nutritional supplementation on quantities of glucose transporters 1 and 4 in sheep granulosa and theca cells. Reproduction 122:947–956

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto N, Ueda-Wakagi M, Sato T, Kawasaki K, Sawada K, Kawabata K, Akagawa M, Ashida H (2015) Measurement of glucose uptake in cultured cells. Curr Protoc Pharmacol 71:12.14.1-12.14.26

    Article  Google Scholar 

  • Zhang C, Xia G, Tsang BK (2011) Interactions of thyroid hormone and FSH in the regulation of rat granulosa cell apoptosis. Front Biosci (Elite Ed) 3:1401–1413

    Google Scholar 

  • Zhang C, Niu W, Wang Z, Wang X, Xia G (2012) The effect of gonadotropin on glucose transport and apoptosis in rat ovary. PLoS One 7:e42406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang C, Wang X, Wang Z, Niu W, Zhu B, Xia G (2013) Effect of different culture systems and 3, 5, 3′-triiodothyronine/follicle-stimulating hormone on preantral follicle development in mice. PLoS One 8:e61947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zheng K, Sulieman FJ, Li J, Wei Q, Xu M, Shi F (2015) Nitric oxide and thyroid hormone receptor alpha 1 contribute to ovarian follicular development in immature hyper- and hypo-thyroid rats. Reprod Biol 15:27–33

    Article  PubMed  Google Scholar 

  • Zhou J, Bievre M, Bondy CA (2000) Reduced GLUT1 expression in Igf1−/− null oocytes and follicles. Growth Horm IGF Res 10:111–117

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. College of Life Science, Capital Normal University, Beijing, 100048, China

      Yu Ding, Ye Tian, Juan Liu, Dai Heng, Baochang Zhu & Cheng Zhang

    2. Department of Laboratory Animal Science, School of Basic Medical Science, Capital Medical University, Beijing, 100069, China

      Meng Guo

    3. Key Laboratory of Fertility Preservation and Maintenance, Ministry of Education, Key Laboratory of Reproduction and Genetics in Ningxia, Department of Histology and Embryology, Ningxia Medical University, Ningxia, 750004, China

      Yanzhou Yang

    Authors
    1. Yu Ding
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Ye Tian
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Meng Guo
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Juan Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Dai Heng
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Baochang Zhu
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Yanzhou Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Cheng Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Yanzhou Yang or Cheng Zhang.

    Ethics declarations

    The funders of this project had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

    Competing interests

    The authors have declared no conflict of interest.

    Additional information

    Yu Ding and Ye Tian contributed equally to this work.

    This work was supported by the National Natural Science Foundation of China (no. 31300958; no. 81560259) and Beijing Natural Science Foundation (no. 5142003). This project was also supported by the Scientific Research Program of Beijing Municipal Commission of Education (KM201610028011).

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    ESM 1

    (TIF 68 kb)

    (GIF 72 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Ding, Y., Tian, Y., Guo, M. et al. Regulation of glucose transport by thyroid hormone in rat ovary. Cell Tissue Res 366, 455–466 (2016). https://doi.org/10.1007/s00441-016-2453-3

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00441-016-2453-3

    Keywords

    Search

    Navigation