Horm Metab Res 2006; 38(4): 253-259
DOI: 10.1055/s-2006-925346
Original
© Georg Thieme Verlag KG Stuttgart · New York

Expression of Corticosteroid-binding Protein in the Human Hypothalamus, Co-localization with Oxytocin and Vasopressin

E.  V.  Sivukhina1, 2 , G.  F.  Jirikowski1 , H.  G.  Bernstein3 , J.  G.  Lewis4 , Z.  Herbert5
  • 1 Department of Anatomy II, Friedrich-Schiller-University, Jena, Germany
  • 2 Department of Histology and Embryology, Kursk State Medical University, Kursk, Russia
  • 3 Department of Psychiatry, Otto-von-Guerike-University, Magdeburg, Germany
  • 4 Steroid and Immunobiochemistry Laboratory, Clinical Biochemistry Unit, Canterbury Health Laboratories, Christchurch, New Zealand
  • 5 Department of Biology II, Neurobiology, Ludwig-Maximilians-University, Munich, Germany
Further Information

Publication History

Received 22 March 2005

Accepted after revision 8 September 2005

Publication Date:
15 May 2006 (online)

Abstract

Corticosteroid-binding globulin, a specific steroid carrier in serum with high binding affinity for glucocorticoids, is expressed in various tissues. In the present study, we describe the immunocytochemical distribution of this protein in neurons and nerve fibers in the human hypothalamus. CBG immunoreactive perikarya and fibers were observed in the paraventricular, supraoptic, and sexual dimorphic nuclei in the perifornical region, as well as in the lateral hypothalamic and medial preoptic areas, the region of the diagonal band, suprachiasmatic and ventromedial nuclei, bed nucleus of the stria terminalis and some epithelial cells from the choroid plexus and ependymal cells. Stained fibers occurred in the median eminence and infundibulum. Double immunostaining revealed a partial co-localization of corticosteroid-binding globulin with oxytocin and, to a lesser extent, with vasopressin in the paraventricular and the supraoptic nuclei. Double immunofluorescence staining showed coexistence of these substances in axonal varicosities in the median eminence. We conclude that neurons of the human hypothalamus are capable of expressing corticosteroid-binding globulin, in part co-localized with the classical neurohypophyseal hormones. The distribution of CBG immunoreactive neurons, which is widespread but limited to specific nuclei, indicates that CBG has many physiological functions that may include neuroendocrine regulation and stress response.

References

  • 1 Hammond G L, Smith C L, Goping I S, Underhill D A, Harley M J, Reventos J, Musto N A, Gunsalus G L, Bardin C W. Primary structure of human corticosteroid binding globulin, deduced from hepatic and pulmonary cDNAs, exhibits homology with serine protease inhibitors.  PNAS. 1987;  84 5153-5157
  • 2 Westphal U. Steroid-Protein Interactions: Monographs on Endocrinology, Vol. 4. Berlin; Springer-Verlag 1971
  • 3 Breuner C W, Orchinik M. Plasma binding proteins as mediators of corticosteroid action in vertebrates.  J Endocrinol. 2002;  175 99-112
  • 4 Nakhla A M, Khan M S, Rosner W. Induction of adenylate cyclase in a mammary carcinoma cell line by human corticosteroid-binding globulin.  Biochem Biophys Res Commun. 1988;  153 1012-1018
  • 5 Miska W, Pena P, Villegas J, Sanchey R. Detection of a CBG-like protein in human Fallopian tube tissue.  Andrologia. 2004;  36 41-46
  • 6 Misao R, Iwagaki S, Sun W S, Fujimoto J, Saio M, Takami T, Tamaya T. Evidence for the synthesis of corticosteroid-binding globulin in human placenta.  Horm Res. 1999;  51 162-167
  • 7 Scrocchi L A, Hearn S A, Han V K, Hammond G L. Corticosteroid-binding globulin biosynthesis in the mouse liver and kidney during postnatal development.  Endocrinology. 1993;  132 910-916
  • 8 Del Mar Grasa M, Cabot C, Adan C, de Matties R, Esteve M, Cinti S, Fernandez J A, Lopez , Remesar X, Alemany A. Corticosteroid-binding globulin synthesis and distribution in rat white adipose tissue.  Mol Cell Biochem. 2001;  228 25-31
  • 9 Misao R, Hori M, Ichigo S, Fujimoto J, Tamaya T. Corticosteroid-binding globulin mRNA levels in human uterine endometrium.  Steroids. 1994;  59 603-607
  • 10 Möpert B, Herbert Z, Caldwell J D, Jirikowski G F. Distribution of corticosteroid-binding globulin in the rat hypothalamus, co-localization with oxytocin and vasopressin.  FENS Abstr. 2004;  vol 2 A089 11
  • 11 Berdusco E TM, Yang K, Hammond G L, Challis J RG. Corticosteroid-binding globulin (CBG) production by hepatic and extra-hepatic sites in the ovine fetus; effects of CBG on glucocorticoid negative feedback on pituitary cells in vitro.  J Endocrinol. 1995;  146 121-130
  • 12 Seralini G E. Regulation factors of corticosteroid-binding globulin: lesson from ontogenesis.  Horm Res. 1996;  45 192-196
  • 13 Hryb D J, Khan M S, Romas N A, Rosner W. Specific binding of human corticosteroid-binding globulin to cell membranes.  PNAS. 1986;  83 3253-3256
  • 14 Singer C J, Khan M S, Rosner W. Characteristics of the binding of corticosteroid-binding globulin to rat cell membranes.  Endocrinology. 1988;  122 89-96
  • 15 Strel’chyonok O A, Avvakumov G V. Interaction of human CBG with cell membranes.  J Steroid Biochem Mol Biol. 1991;  40 795-803
  • 16 Maitra U S, Khan M S, Rosner W. Corticosteroid-binding globulin receptor of the rat hepatic membrane - solubilization, partial characterization, and the effect of steroids on binding.  Endocrinology. 1993;  133 1817-1822
  • 17 Schwarz S, Pohl P. Steroid hormones and steroid hormone binding globulins in cerebrospinal fluid studied in individuals with intact and with disturbed blood-cerebrospinal fluid barrier.  Neuroendocrinology. 1992;  55 174-182
  • 18 Predine J, Brailly S, Delaporte P, Milgrom E. Protein binding of cortisol in human cerebrospinal fluid.  J Clin Endocrinol Metab. 1984;  58 6-11
  • 19 Dierickx K, Vandesande F. Immunocytochemical localization of the vasopressinergic and the oxytocinergic neurons in the human hypothalamus.  Cell Tissue Res. 1977;  184 15-27
  • 20 Swaab D F. Neurobiology and neuropathology of the human hypothalamus. In: Björklund A, Hökfelt T (eds) Handbook of Chemical Neuroanatomy. Amsterdam; Elsevier 1997 Vol. 13, part 1: 39-137
  • 21 Lederis K, Pittman Q J, Kasting N W, Veale W, Cooper K E. Central neuromodulatory role of vasopressin in antipyresis and in febrile convulsions.  Biomed Res. 1982;  3 1-5
  • 22 Pittman Q J, Lawrence D, McLean L. Central effects of arginine vasopressin on blood pressure in rats.  Endocrinology. 1982;  110 1058-1060
  • 23 De Goeij D CE, Kvetnansky R, Whitnall M H, Jezova D, Berkenbosch F, Tilders F JH. Repeated stress-induced activation of corticotropin-releasing factor neurons enhances vasopressin stores and colocalization with CRF in the median eminence of rats.  Neuroendocrinology. 1991;  53 150-159
  • 24 Volpi S, Rabadan-Diehl C, Aguilera G. Vasopressinergic regulation of the hypothalamic pituitary adrenal axis and stress adaptation.  Stress. 2004;  7 75-83
  • 25 Aguilera G. Regulation of pituitary ACTH secretion during chronic stress.  Front Neuroendocrinol. 1994;  15 321-350
  • 26 Chrousos G P. Ultradian, circadian, and stress-related hypothalamic-pituitary-adrenal axis activity - a dynamic digital-to-analog modulation.  Endocrinology. 1998;  139 437-440
  • 27 Pedersen C A, Ascher J A, Monroe Y L, Prange A J. Oxytocin induces maternal behaviour in virgin female rats.  Science. 1982;  216 648-649
  • 28 Fahrbach S E, Morrell J I, Pfaff D W. Possible role of endogenous oxytocin in estrogen-facilitated maternal behaviour in rats.  Neuroendocrinology. 1985;  40 526-532
  • 29 Caldwell J D, Jirikowski G F, Greer E R, Pedersen C A. Medial preoptic area oxytocin and female sexual receptivity.  Behav Neurosci. 1989;  103 655-662
  • 30 Fehm-Wohlsdorf G, Born J, Voigt K H, Fehm H L. Human memory and neurohypophyseal hormone: opposite effects of vasopressin and oxytocin.  Psychoneuroendocrinology. 1984;  9 285-292
  • 31 Lang R E, Heil J W, Ganten D, Hermann K, Unger T, Rascher W. Oxytocin unlike vasopressin is a stress hormone in the rat.  Neuroendocrinology. 1983;  37 314-316
  • 32 Jezova D, Skultetyova I, Tokarev D I, Bakos P, Vigas M. Vasopressin and oxytocin in stress.  Ann N Y Acad Sci. 1995;  771 192-203
  • 33 Wotjak C T, Naruo T, Muraoka S, Simchen R, Landgraf R, Engelmann M. Forced swimming stimulates the expression of vasopressin and oxytocin in magnocellular neurons of the rat hypothalamic paraventricular nucleus.  Eur J Neurosci. 2001;  13 2273-2281
  • 34 Jirikowski G F, McGimsey W C, Caldwell J D, Sar M. Distribution of oxytocinergic glucocorticoid target neurons in the rat hypothalamus.  Horm Metab Res. 1993;  25 543-544
  • 35 Jirikowski G F, Ramalho-Ortigao J F, Kesse K W, Bloom F E. In situ hybridization of semithin Epon sections with BrdU labeled oligonucleotide probes.  Histochemistry. 1990;  94 187-190
  • 36 Lewis J G, Lewis M G, Elder P A. An enzyme-linked immunosorbent assay for corticosteroid-binding globulin using monoclonal and polyclonal antibodies: decline in CBG following synthetic ACTH.  Clin Chim Acta. 2003;  328 121-128
  • 37 Mai J K, Assheuer J, Paxinos G. Atlas of the human brain. Second edition. San Diego; Academic Press 2004
  • 38 Pardridge W M, Eisenberg J, Fierer G, Kuhn R W. CBG does not restrict blood-brain barrier corticosterone transport in rabbits.  Am J Physiol. 1986;  251 E204-208
  • 39 Fuxe K, Wikström A C, Okret S, Agnati L F, Härfstrand A, Yu Z Y, Granholm L, Zoli M, Vale W, Gustafsson J A. Mapping of glucocorticoid receptor immunoreactive neurons in the rat tel- and diencephalon using a monoclonal antibody against rat liver GR.  Endocrinology. 1985;  117 1803-1812
  • 40 Reul J M, de Kloet E R. Two receptor systems for corticosterone in rat brain: microdistribution and different occupation.  Endocrinology. 1985;  117 2505-2511
  • 41 Chao H M, Choo P H, McEwen B S. Glucocorticoid and mineralocorticoid receptor mRNA expression in rat brain.  Neuroendocrinology. 1989;  50 365-371
  • 42 Herman J P. Regulation of adrenocorticosteroid receptor mRNA expression in the central nervous system.  Cell Mol Neurobio. 1993;  13 349-372
  • 43 Ozawa H, Ito T, Ochiai I, Kawata M. Cellular localization and distribution of glucocorticoid receptor immunoreactivity and the expression of glucocorticoid receptor messenger RNA in rat pituitary gland. A combined double immunohistochemistry study and in situ hybridization histochemical analysis.  Cell Tissue Res. 1999;  295 207-214
  • 44 Gustafsson J A. Steroids and the scientist.  Mol Endocrinol. 2005;  19 1412-1417
  • 45 Herbert Z, Jirikowski G F, Petrusz P, Englöf I, Caldwell J D. Distribution of androgen-binding protein in the rat hypothalamo-neurohypophyseal system, co-localization with oxytocin.  Brain Res. 2003;  992 151-158
  • 46 Morris J F, Pow D V. Widespread release of peptides in the central nervous system: quantitation of tannic acid-captured exocytoses.  Anat Rec. 1991;  231 437-445
  • 47 Orchinik M, Hastings N, Witt D, McEwen B S. High affinity binding of corticosterone to mammalian neuronal membranes: possible role of corticosteroid binding globulin.  J Steroid Biochem Mol Biol. 1997;  60 229-236
  • 48 Rosner W. Plasma steroid binding proteins.  Endocrinol Metab Clin North Am. 1991;  20 697-720

Dr. Elena V. Sivukhina, PhD

Department of Anatomy II

Friedrich-Schiller-University Jena · Teichgraben 7 · 07740 Jena · Germany

Fax: +49 (3641) 93 85 52

Email: esiv@mti.uni-jena.de

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