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Functional state of adenylyl cyclase signaling system in reproductive tissues of rats with experimental type-1 diabetes

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Abstract

Type-1 diabetes mellitus (DM) leads to numerous disturbances in the male and female reproductive systems. As was shown previously, one of the main causes of the development of complications in DM is a change in the sensitivity of the adenylyl cyclase signaling system (ACSS) to hormones. The aim of this work consisted in detection of disturbances in the hormone-regulated ACSS in reproductive system of rats with experimental type-1 DM (EDM1) caused by administration of streptozotocin. It has been shown that, in the testes of male rats with 5-day-long EDM1 the stimulating effects of human chorionic gonadotropin (HCG) and PACAP-38 on adenylyl cyclase (AC) and the GTP binding of G proteins are decreased considerably. In the uteri of female rats with EDM1 the effects of relaxin, PACAP-38, and biogenic amines are markedly decreased, whereas in ovaries only the effects of HCG are decreased. In all studied tissues of rats with EDM1 the attenuation of somatostatin inhibitory effects was observed, while in the uterus the inhibitory effects of serotonin and adrenalin were also decreased. Thus, in the reproductive tissues of rats with EDM1, the hormone regulatory effects on ACSS are decreased, especially the effect of HCG and the hormones, AC-inhibitors. We believe that the sensitivity of ACSS to hormones in EDM1 underlies the development of pathological changes in the reproductive system of diabetic rats under the conditions of hyperglycemia and insulin deficiency characteristic of type-1 DM.

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Abbreviations

AC:

adenylyl cyclase

ACSS:

adenylyl cyclase signaling system

DM:

diabetes mellitus

HCG:

human chorionic gonadotropin

EDM1:

experimental type-1 diabetes mellitus

Gs and Gi proteins:

G proteins of stimulatory and inhibitory types, respectively

GppNHp:

β, γ-imidoguanosine-5′-triphosphate

PACAP:

pituitary adenylyl cyclase activating polypeptide

References

  • Ballester, J., Munoz, M.C., Dominguez, J., Palomo, M.J., Rivera, M., Rigau, T., Guinovart, J.J., and Rodriguez-Gil, J.E., Tungstate Administration Improves the Sexual and Reproductive Function in Female Rats with Streptozotocin-Induced Diabetes, Hum. Reprod., 2007, vol. 22, pp. 2128–2135.

    Article  CAS  PubMed  Google Scholar 

  • Ballester, J., Munoz, M.C., Dominguez, J., Rigau, T., Guinovart, J.J., and Rodriguez-Gil, J.E., Insulin-Dependent Diabetes Affects Testicular Function by FSH- and LH-Linked Mechanisms, J. Androl., 2004, vol. 25, pp. 706–719.

    CAS  PubMed  Google Scholar 

  • Bestetti, G.E., Junker, U., Locatelli, V., and Rossi, G.L., Continuous Subtherapeutic Insulin Counteracts Hypothalamo-Pituitary-Gonadal Alterations in Diabetic Rats, Diabetes, 1987, vol. 36, pp. 1315–1319.

    Article  CAS  PubMed  Google Scholar 

  • Bhatia, V., Chaudhuri, A., Tomar, R., Dhindsa, S., Ghanim, H., and Dandona, P., Low Testosterone and High C-Reactive Protein Concentrations Predict Low Hematorcrit in Type 2 Diabetes, Diabetes Care, 2006, vol. 29, pp. 2289–2294.

    Article  CAS  PubMed  Google Scholar 

  • Codner, E., Mook-Kanamori, D., Bazaes, R.A., Unanue, N., Sovino, H., Ugarte, F., Avila, A., Iniguez, G., and Cassorla, F., Ovarian Function During Puberty in Girls with Type 1 Diabetes Mellitus: Response to Leuprolide, J. Clin. Endocrinol. Metab., 2005, vol. 90, pp. 3939–3945.

    Article  CAS  PubMed  Google Scholar 

  • Costagliola, S., Urizar, E., Mendive, F., and Vassart, G., Specificity and Promiscuity of Gonadotropin Receptors, Reproduction, 2005, vol. 130, pp. 275–281.

    Article  CAS  PubMed  Google Scholar 

  • De Hertogh, R., Vandeheyden, I., Pampfer, S., Robin, D., and Delcourt, J., Maternal Insulin Treatment Improves Pre-Implantation Embryo Development in Diabetic Rats, Diabetologia, 1992, vol. 35, pp. 406–408.

    Article  PubMed  Google Scholar 

  • Gando, S., Hattori, Y., Akaishi, Y., Nishihira, J., and Kanno, M., Impaired Contractile Response to β Adrenoreceptor Stimulation in Diabetic Rat Hearts: Alterations in β Adrenoreceptors-G Protein-Adenylate Cyclase System and Phospholamban Phosphorylation, J. Pharmacol. Exp. Ther., 1997, vol. 282, pp. 475–484.

    CAS  PubMed  Google Scholar 

  • Gawler, D., Milligan, G., Spiegel, A.M., Unson, C.G., and Houslay, M.D., Abolition of Expression of Inhibitory Guanine Nucleotide Regulatory Protein Gi Activity in Diabetes, Nature, 1987, vol. 327, pp. 229–232.

    Article  CAS  PubMed  Google Scholar 

  • Hashim, S. Li Y., Nagakura, A., Takeo, S., and Anand-Srivastava, M.B., Modulation of G-Ptotein Expression and Adenylyl Cyclase Signaling by High Glucose in Vascular Smooth Muscle, Cardiovasc. Res., 2004, vol. 63, pp. 709–718.

    Article  CAS  PubMed  Google Scholar 

  • Hashim, S., Li, Y.Y., Wang, R., and Anand-Srivastava, M.B., Streptozotocin-Induced Diabetes Impairs G-Protein Linked Signal Transduction in Vascular Smooth Muscle, Mol. Cell. Biochem., 2002, vol. 240, pp. 57–65.

    Article  CAS  PubMed  Google Scholar 

  • Hemmings, S.J. and Spafford, D., Neonatal STZ Model of Type II Diabetes Mellitus in the Fischer 344 Rat: Characteristics and Assessment of the Status of the Hepatic Adrenergic Receptors, Int. J. Biochem. Cell Biol., 2000, vol. 32, pp. 905–919.

    Article  CAS  PubMed  Google Scholar 

  • Hughes, S.J., Hollingswirth, M., and Elliott, K.R., The Role of a Camp-Dependent Pathway in the Uterine Relaxant Action of Relaxin in Rats, J. Reprod. Fertil., 1997, vol. 109, pp. 289–296.

    Article  CAS  PubMed  Google Scholar 

  • Krantic, S. and Benahmed, M., Somatostatin Inhibits Follicle-Stimulating Hormoneinduced Adenylyl Cyclase Activity and Proliferation in Immature Porcine Sertoli Cell via sst2 Receptor, Biol. Reprod., 2000, vol. 62, pp. 1835–1843.

    Article  CAS  PubMed  Google Scholar 

  • Lam, D.D. and Heisler, L.K., Serotonin and Energy Balance: Molecular Mechanisms and Implications for Type 2 Diabetes, Expert. Rev. Mol. Med., 2007, vol. 9, pp. 1–24.

    Article  PubMed  Google Scholar 

  • Leatherland, J.F., Lin, L., and Renaud, R., Effect of Glutamate and Somatostatin-14 on Basal and Camp-Stimulated Steroidogenesis by Rainbow Trout (Oncorhynchus mykiss) Ovarian Follicles, in Vitro, Comp. Biochem. Physiol., 2005, vol. 140, pp. 647–656.

    Article  CAS  Google Scholar 

  • Lee, J., Park, H.J., Choi, H.S., Kwon, H.B., Arimura, A., Lee, B.J., Choi, W.S, and Chun, S.Y., Gonadotropin Stimulation of Pituitary Adenylate Cyclase-Activating Polypeptide (Pacap) Messenger Ribonucleic Acid in the Rat Ovary and the Role of Pacap as a Follicle Survival Factor, Endocrinology, 1999, vol. 140, pp. 818–826.

    Article  CAS  PubMed  Google Scholar 

  • Li, M. and Arimura, A., Neuropeptides of the Pituitary Adenylate Cyclase-Activating Polypeptide/Vasoactive Intestinal Polypeptide/Growth Hormone-Releasing Hormone/Secretin Family in Testis, Endocrine, 2003, vol. 20, pp. 201–214.

    Article  CAS  PubMed  Google Scholar 

  • Livingstone, C., Mclellan, A.R., Mcgregor, M., Wilson, A., Connel, J.M., Small, M., Milligan, G., Paterson, K.R., and Houslay, M.D., Altered G-Protein Expression and Daenylyl Cyclase Activity in Platelets of Non-Insulin-Dependent Diabetic (NIDDM) Male Subjects, Biochem. Biophys. Acta, 1991, vol. 1096, pp. 127–133.

    CAS  PubMed  Google Scholar 

  • Munoz, M.C., Barbera, A., Dominguez, J., Fernandez-Alvarez, J., Gomis, R.R., and Guinovart, J.J., Effects of Tungstate, a New Potential Oral Antidiabetic Agent, on Zucker Diabetic Fatty Rats, Diabetes, 2001, vol. 50, pp. 131–138.

    Article  CAS  PubMed  Google Scholar 

  • Palmer, T.M., Taberner, P.V., and Houslay, M.D., Alterations in G Protein Expression, Gi Finction and Stimulatory Receptor-Mediated Regulation of Adipocyte Adenylyl Cyclase in a Model of Insulin-Resistant Diabetes with Obesity, Cell. Signal., 1992, vol. 4, pp. 365–377.

    Article  CAS  PubMed  Google Scholar 

  • Shpakov, A., Pertseva, M., Kuznetsova, L., and Plesneva, S., A Novel Adenylate Cyclase, Signaling Mechanism of Relaxin H2 Action, Ann. N.Y. Acad. Sci., 2005c, vol. 1041, pp. 305–307.

    Article  CAS  PubMed  Google Scholar 

  • Shpakov, A.O., Gur’yanov, I.A., Kuznetsova, L.A., Plesneva, S.A., Korol’Kov, V.I., Pertseva, M.N., and Vlasov, G.P., The Use of C-Terminal Peptides of α-Subunits of G Proteins to Study Their Functional Coupling to Biogenic Amine Receptors in Rat and Molluscan Tissues, Biol. Membr., 2004, vol. 21, no. 6, pp. 441–450.

    Google Scholar 

  • Shpakov, A.O., Kuznetsova, L.A., Plesneva, S.A., and Pertseva, M.N., Molecular Mechanisms of Changes in the Sensitivity of Adenylyl Cyclase Signaling System to Biogenic Amines in Streptozotocin-Induced Diabetes, Byul. Eksper. Biol., 2005a, vol. 140, no. 9, pp. 286–290.

    Google Scholar 

  • Shpakov, A.O., Kuznetsova, L.A., Plesneva, S.A., and Pertseva, M.N., The Disturbance of the Transduction of Adenylyl Cyclase Inhibiting Hormonal Signal in Myocardium and Brain of Rats with Experimental Type II Diabetes, Tsitologiia, 2007b, vol. 49, no. 6, pp. 442–450.

    CAS  PubMed  Google Scholar 

  • Shpakov, A.O., Kuznetsova, L.A., Plesneva, S.A., Bondareva, V.M., Gur’yanov, I.A., Vlasov, G.P., and Pertseva, M.N., Decrease in Functional Activity of G-Proteins Hormone-Sensitive Adenylate Cyclase Signaling System, During Experimental Type II Diabetes Mellitus, Byul. Eksp. Biol. Med., 2006a, vol. 142, no. 12, pp. 641–645.

    Google Scholar 

  • Shpakov, A.O., Kuznetsova, L.A., Plesneva, S.A., Gur’yanov, I.A., Vlasov, G.P., and Pertseva, M.N., Identification of Lesions in the Hormone-Sensitive AC System in Tissues of Rats with Type 1 and 2 Diabetes Mellitus Using Functional Probes and Synthetic Nanosize Peptides, Tekhn. Zhiv. Sist., 2007a, vol. 4, nos. 5–6, pp. 96–108.

    CAS  Google Scholar 

  • Shpakov, A.O., Kuznetsova, L.A., Plesneva, S.A., Kolychev, A.P., Bondareva, V.M., Chistyakova, O.V., and Pertseva, M.N., Functional Defects in Adenylyl Cyclase Signaling Mechanisms of Insulin and Relaxin Action in Skeletal Muscles of Rat with Streptozotocin Type 1 Diabetes, Cent. Eur. J. Biol., 2006b, vol. 1, pp. 530–544.

    Article  CAS  Google Scholar 

  • Shpakov, A.O., Pertseva, M.N., Gur’yanov, I.A., and Vlasov, G.P., The Effect of Peptides, Derivatives of the Third Cytoplasmic Loop of Type 1 Relaxin Receptor on the Stimulation of GTP-Binding Activity of G Proteins by Relaxin, Biol. Membr., 2005b, vol. 22, no. 6, pp. 435–442.

    Google Scholar 

  • Sudha, S., Valli, G., Julie, M.P., Arunakaran, J., Govindarajulu, P., and Balasubramanian, K., Influence of Streptozotocin-Induced Diabetes and Insulin Treatment on the Pituitary-Testicular Axis during Sezual Maturation in Rats, Exp. Clin. Endocrinol. Diabetes, 2000, vol. 108, pp. 14–20.

    CAS  PubMed  Google Scholar 

  • Tanaka, M., Nakaya, S., Kumai, T., Watanabe, M., Matsumoto, N., and Kobayashi, S., Impaired Testicular Function in Rats with Diet-Induced Hypercholesterolemia and/or Streptozotocin-Induced Diabetes Mellitus, Endocr. Res., 2001, vol. 27, pp. 109–117.

    Article  CAS  PubMed  Google Scholar 

  • Vaccari, S., Latini, S., Barberi, M. Teti, A., Stefanini, M., and Canipari, R., Characterization and Expression of Different Pituitary Adenylate Cyclase-Activating Polypeptide/Vasoactive Intestinal Polypeptide Receptors in Rat Ovarian Follicles, J. Endocrinol., 2006, vol. 191, pp. 287–299.

    Article  CAS  PubMed  Google Scholar 

  • Weber, L.P. and Macleod, K.M., Influence of Streptozotocin Diabetes on the Alpha-1 Adrenoreceptor and Associated G Proteins in Rat Arteries, J. Pharmacol. Exp. Ther., 1997, vol. 283, pp. 1469–1478.

    CAS  PubMed  Google Scholar 

  • Wichelhaus, A., Russ, M., Petersen, S., and Eckel, J., G Protein Expression and Adenylate Cyclase Regulation in Ventricular Cardiomyocytes from STZ-Diabetic Rats, Am. J. Physiol., 1994, vol. 267, pp. 548–555.

    Google Scholar 

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    A. O. Shpakov, V. M. Bondareva & O. V. Chistyakova

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  1. A. O. Shpakov
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  2. V. M. Bondareva
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  3. O. V. Chistyakova
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Correspondence to A. O. Shpakov.

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Original Russian Text © A.O. Shpakov, V.M. Bondareva, O.V. Chistyakova, 2010, published in Tsitologiya, Vol. 52, No. 2, 2010, pp. 177–183.

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Shpakov, A.O., Bondareva, V.M. & Chistyakova, O.V. Functional state of adenylyl cyclase signaling system in reproductive tissues of rats with experimental type-1 diabetes. Cell Tiss. Biol. 4, 208–214 (2010). https://doi.org/10.1134/S1990519X10020112

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