Changes of Sex Hormone-binding Globulin/SHBG Expression in the Hypothalamo-hypophyseal System of Rats During Pregnancy, Parturition and Lactation

Abstract

Sex hormone-binding globulin (SHBG) is expressed in hypothalamic magnocellular neurons. High co-localization rates of SHBG with oxytocin have been observed in the hypothalamus, indicating that SHBG plays a role in pregnancy, parturition and lactation. Further studies have shown that hypothalamic SHBG expression is malleable to changing steroid conditions. In this study, we have examined SHBG levels in the supraoptic and paraventricular hypothalamic nuclei and in the posterior pituitary lobe of late pregnant, parturient and early lactating rats by in situ hybridization, immunocytochemistry, and ELISA. Immunocytochemical and biochemical analysis showed that the SHBG levels increased during late pregnancy in hypothalamic nuclei. During parturition, SHBG levels fell in the magnocellular nuclei but increased in the posterior pituitary lobe. SHBG levels increase again during lactation. At day six of lactation, there was no significant difference in SHBG levels compared to normal cycling female rats, which served as control in this study. In situ hybridization showed increased SHBG mRNA signal during late pregnancy. The highest SHBG expression was observed during parturition. Our data indicate that hypothalamic SHBG expression changes during pregnancy, parturition and lactation, parallel to ovarian steroid and co-localized OT levels. This may in part be linked to known steroid actions on synthesis and secretion of magnocellular hypothalamic peptide hormones, important for the control of parturition and lactation.

Supraoptic nucleus - paraventricular nucleus - parturition - magnocellular hypothalamic neurons - steroid actions - oxytocin

References

• 1 Herbert Z, Jirikowski G F, Petrusz P, Englof I, Caldwell J D. Distribution of androgen binding globulin in the rat hypothalamo-hypophysial system, co-localization with oxytocin.  Brain Res. 2003;  992 151-158
• 2 Herbert Z, Gothe S, Caldwell J D, Petrusz P, Peuckert P, Jirikowski G F. Identification of sex hormone-binding globulin in the human hypothalamus.  Neuroendocrinol. 2005;  81 287-293
• 3 Wang Y M, Bayliss D A, Millhorn D E, Petrusz P, Joseph D R. The androgen-binding protein gene is expressed in male and female rat brain.  Endocrinology. 1990;  127 3124-3130
• 4 Leng G, Caquineau C, Sabatier N. Regulation of oxytocin secretion.  Vitam Horm. 2005;  71 27-58
• 5 Herbert Z, Pollak E, Molnar L, Caldwell J D, Jirikowski G F. Co-transport of sex hormone binding globulin/SHBG with oxytocin in transport vesicles of the hypothalamo-hypophyseal system.  Horm Metab Res. 2006;  in press
• 6 Caldwell J D, Moe B D, Hoang J, Nguyen T. Sex hormone binding globulin stimulates female sexual receptivity.  Brain Res. 2000;  874 24-29
• 7 Caldwell J D. Evidence of sex hormone binding globulin binding sites in the medial preoptic area and hypothalamus.  Horm Metab Res. 2001;  33 7-9
• 8 Fortunati N. Sex hormone-binding globulin: Not only a transport protein. What news is around the corner?.  J Endocrinol Invest. 1999;  22 223-234
• 9 Danzo B J, Cooper T G, Orgebin-Crist M C. Androgen binding protein (ABP) in fluids collected from the rete testis and cauda epididymidis of sexually mature and immature rabbits and observations on morphological changes in the epididymis following ligation of the ductuli efferentes.  Biol Reprod. 1977;  17 64-77
• 10 Rosner W, Hryb D J, Khan M S, Nakhla A M, Romas N A. Sex hormone-binding globulin mediates steroid hormone signal transduction at the plasma membrane.  J Steroid Biochem Mol Biol. 1999;  69 481-485
• 11 Jirikowski G F, Ramalho Ortigao F J, Lindl T, Seliger H. Immunocytochemistry of 5-bromo-2’-deoxyuridine labeled oligonucleotide probes. A novel technique for in situ hybridization.  Histochemistry. 1989b;  91 51-53
• 12 Becchis M, Sullivan P M, Ordronneau P, Petrusz P, Joseph D R. Distribution of immunoreactive androgen-binding protein/sex hormone-binding globulin in tissues of the fetal rat.  Steroids. 1996;  61 392-400
• 13 Reventos J, Hammond G L, Crozat A, Brooks D E, Gunsalus G L, Bardin C W, Musto N A. Hormonal regulation of rat androgen-binding protein (ABP) messenger ribonucleic acid and homology of human testosterone-estradiol-binding globulin and ABP complementary deoxyribonucleic acids.  Mol Endocrinol. 1988;  2 125-132
• 14 Jirikowski G F. SOFIA, A Superior approach for high sensitivity immunoassays.  Biomed Prod. 1993;  7193 105-109
• 15 Gao G, Herbert Z, Kong J, Wu D, Gabrielson N, Jirikowski G F, Caldwell J D. Estradiol control of estradiol binding proteins and levels in the medial preoptic area, medial hypothalamus and pituitary.  Neuroendocrinology. 2003;  78 61-71
• 16 Wang Y M, Bayliss D A, Millhorn D E, Petrusz P, Joseph D R. The androgen-binding protein gene is expressed in male and female rat brain.  Endocrinol. 1990;  127 3124-3130
• 17 Jirikowski G F, Herbert Z, Petrusz P, Sendemir E, Caldwell J D. Co-expression of vasopressin and androgen-binding protein in the rat hypothalamus.  J Chem Neuroanat. 2005;  29 233-237
• 18 Jirikowski G F, Caldwell J D, Pedersen C A, Stumpf W E. Estradiol influences oxytocin-immunoreactive brain systems.  Neuroscience. 1988;  25 237-248
• 19 Caldwell J D, Hoefle S, Englof I. Sex hormone binding globulin facilitates female sexual receptivity except when coupled to dihydrotestosterone.  Brain Res. 2002;  948 102-107
• 20 Caldwell J D, Moe B D. Conjugated estrodiol increases female sexual receptivity in response to oxytocin infused into the medial preoptic area and medial basal hypothalamus.  Horm Behav. 1999;  35 38-46
• 21 Buijs R M, de Vries G J, van Leeuwen F W, Swaab D F. Vasopressin and oxytocin: distribution and putative functions in the brain. Prog.  Brain Res. 1983;  60 115-122
• 22 Florio P, Woods R J, Genazzani A R, Lowry P J, Petraglia F. Changes in amniotic fluid immunoreactive corticotropin-releasing factor (CRF) and CRF-binding protein levels in pregnant women at term and during labor.  J Clin Endocrinol Metab. 1997;  82 835-838
• 23 Stumpf W E, Sar M, Keefer D A. Atlas of estrogen target cells in the rat brain. In: Stumpf WE, Grant LD (eds) Anatomical Neuroendocrinology. Basel; Karger 1975: 104-119
• 24 Perez S E, Chen E Y, Mufson E J. Distribution of estrogen receptor alpha and beta immunoreactive profiles in the postnatal rat brain.  Brain Res Dev Brain Res. 2003;  145 117-139
• 25 Vigh B, Vigh-Teichmann I. Comparison of the ultrastructure of cerebrospinal-fluid-contact neurons and pinealocytes in mammals.  Verh Anat Ges. 1975;  69 453-461
• 26 Fassler R, Schwarz S, Pohl P. Demonstration of sex hormone binding globulin in human cerebrospinal fluid.  Clin Endocrinol (Oxf). 1985;  23 349-359
• 27 Jirikowski G F, Caldwell J D, Pilgrim C, Stumpf W E, Pedersen C A. Changes in immunostaining for oxytocin in the forebrain of the female rat during late pregnancy, parturition and early lactation.  Cell Tissue Res. 1989a;  256 411-417
• 28 Ganten D, Pfaff D. Neurobiology of oxytocin. In: Ganten D, Pfaff D (eds) Current topics in neuroendocrinology. Heidelberg; Springer 1986: 1-175
• 29 Breuner C W, Orchinik M. Plasmabinding proteins as mediators of Corticosteroid action in vertebrates.  J Endocrinol.. 2002;  175 99-112