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Horm Metab Res 2004; 36(1): 27-33
DOI: 10.1055/s-2004-814198
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Effects of Undernutrition on Serum and Testicular Testosterone Levels and Sexual Function in Adult Rats

A.  Marcelly de Souza Santos1 , M.  R.  Ferraz2 , C.  V.  Teixeira1 , F.  J.  B.  Sampaio1 , C.  da Fonte Ramos1
  • 1Urogenital Research Unit, State University of Rio de Janeiro, Rio de Janeiro, Brazil
  • 2Department of Pharmacology and Psicobiology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
Further Information

Publication History

Received 30 December 2002

Accepted after revision 20 June 2003

Publication Date:
25 February 2004 (online)

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Abstract

The aim of this study was to evaluate testosterone concentrations, sexual behavior, and androgen receptor protein level in the testes of rats submitted to protein- and energy-restricted diets during 30 days. Adult male Wistar rats were assigned to one of the following groups: (C) control, diet with 23 % of protein; (PR) protein-restricted, diet with 8 % of protein; (ER) energy-restricted, diet with 23 % of protein in restricted quantities. Mount number, ejaculation latencies and copulatory efficiency were evaluated to determine sexual behavior. At the end of the experiment, the animals were sacrificed to determine serum and testicular testosterone concentrations as well as testicular androgen receptor protein level. Compared to the C group, the ER group presented a significant decrease in body (36 %), testis (20 %) and epididymis (14 %) weights in serum (78 %) and testicular (68 %) testosterone concentrations as well as in copulatory efficiency (26 %). On the other hand, the ER group presented a significant increase in mount number (114 %) and ejaculatory latency (62 %). The androgen receptor protein levels were significantly reduced in both PR and ER groups (41 % and 74 %, respectively). This is the first paper to demonstrate that the effect of undernutrition on reproduction is not related to reduced protein intake but caloric restriction. Also, in caloric restriction, there is a relationship between sex behavior, androgen receptors, and testosterone concentration.

Key words

Malnutrition · Rats · Androgen receptor · Testosterone · Sex behavior

References

  • 1 Carson-Jurica M A, Schrader W T, O’Malley B W. Steroid receptor family: structure and functions.  Endocr Rev. 1990;  11 201-220
    PubMedGoogle Scholar
  • 2 Zhou Z X, Wong C I, Sar M, Wilson E M. The androgen receptor: an overview.  Recent Prog Horm Res. 1994;  49 249-274
    PubMedGoogle Scholar
  • 3 Lindzey J, Kumar M V, Grossman M, Young C, Tindall D J. Molecular mechanisms of androgen action.  Vitam Horm. 1994;  49 383-432
    PubMedGoogle Scholar
  • 4 Burnstein K L, Cidlowski J A. The down side of glucocorticoid receptor regulation.  Mol Cell Endocrinol. 1992;  83 C1-8
    CrossrefPubMedGoogle Scholar
  • 5 Quarmby V E, Yarbrough W G, Lubahn D B, French F S, Wilson E M. Autologous down-regulation of androgen receptor messenger ribonucleic acid.  Mol Endocrinol. 1990;  4 22-28
    CrossrefPubMedGoogle Scholar
  • 6 Krongrad A, Wilson C M, Wilson J D, Allman D R, McPhaul M J. Androgen increases androgen receptor protein while decreasing receptor mRNA in LNCaP cells.  Mol Cell Endocrinol. 1991;  76 79-88
    CrossrefPubMedGoogle Scholar
  • 7 Hackenberg R, Hawighorst T, Filmer A, Slater E P, Bock K, Beato M, Schulz K D. Regulation of androgen receptor mRNA and protein level by steroid hormones in human mammary cancer cells.  J Steroid Biochem Mol Biol. 1992;  43 599-607
    CrossrefPubMedGoogle Scholar
  • 8 Wolf D A, Herzinger T, Hermeking H, Blaschke D, Hürz W. Transcriptional and posttranscriptional regulation of human androgen receptor expression by androgen.  Mol Endocrinol. 1993;  7 924-936
    CrossrefPubMedGoogle Scholar
  • 9 Gonzalez-Cadavid N F, Vernet D, Navarro A F, Rodriguez A J, Swerdloff R S, Rajfer J. Up-regulation of the levels of androgen receptor and its mRNA by androgens in smooth-muscle cells from rat penis.  Mol Cell Endocrinol. 1993;  90 219-229
    CrossrefPubMedGoogle Scholar
  • 10 Kerr J E, Allore R J, Beck S G, Handa R J. Distribution and hormonal regulation of androgen receptor (AR) and AR messenger ribonucleic acid in the rat hippocampus.  Endocrinology. 1995;  136 3213-3221
    CrossrefPubMedGoogle Scholar
  • 11 Nastiuk K L, Clayton D F. Seasonal and tissue-specific regulation of canary androgen receptor messenger ribonucleic acid.  Endocrinol. 1994;  134 640-649
    CrossrefPubMedGoogle Scholar
  • 12 Dai J L, Maiorino C A, Gkonos P J, Burnstein K L. Androgenic up-regulation of androgen receptor cDNA expression in androgen-independent prostate cancer cells.  Steroids. 1996;  61 531-539
    CrossrefPubMedGoogle Scholar
  • 13 Sachs B D, Barfield R T. Temporal patterning of sexual behavior in the male rat.  J Comp Physiol Psych. 1970;  73 359-364
    PubMedGoogle Scholar
  • 14 Ferraz M R, Ferraz M MD, Santos R. How REM sleep deprivation and amantadine affects male rat sexual behavior.  Pharmacol biochem Behav. 2001;  69 325-332
    CrossrefPubMedGoogle Scholar
  • 15 Rocha-de-Melo A P, Guedes R CA. Spreading depression is facilitated in adult rats previously submitted to short episodes of malnutrition during the lactation period.  Braz J Med Biol Res. 1997;  30 663-669
    PubMedGoogle Scholar
  • 16 Ramos C F, Teixeira C V, Passos M CF, Pazos-Moura C C, Lisboa P C, Curty F H, Moura E G. Low-protein diet changes thyroid function in lactating rats.  P.S.E.B.M.. 2000;  224 256-263
    CrossrefPubMedGoogle Scholar
  • 17 Cónsole G M, Jurado S B, Oyhenart E, Ferese C, Pucciarelli H, Gómez Dumm C LA. Morphometric and ultrastructural analysis of different pituitary cell populations in undernourished.  Braz Med Biol Res. 2001;  34 65-74
    PubMedGoogle Scholar
  • 18 Desjardins C, Lopez M J. Environmental cues evoke differential responses in pituitary-testicular function in deer mice.  Endocrinol. 1983;  112 1398-1406
    PubMedGoogle Scholar
  • 19 Chik C L, Ho A K, Brown G M. Effect of pinealectomy on the undernutrition-induced suppression of the reproductive axis in rats.  Acta Endocrinol (Copenh). 1989;  120 569-573
    PubMedGoogle Scholar
  • 20 Grewal T, Mickeelsen D, Hafs H D. Androgen secretion and spermatogenesis in rat following semistarvation.  Proc Soc Exp Biol Med. 1971;  138 723-729
    PubMedGoogle Scholar
  • 21 Young K A, Zirkin B R, Nelson R J. Testicular regression in response to food restriction and short photoperiod in White-Footed Mice (Peromyscus leucopus) is mediated by apoptosis.  Biol Reprod. 2000;  62 347-354
    PubMedGoogle Scholar
  • 22 Howland B E. The influence of feed restriction and subsequent refeeding on gonadotrophin secretion and serum testosterone levels in male rats.  J Reprod Fertil. 1975;  44 429-436
    PubMedGoogle Scholar
  • 23 Herbert D C. Morphology of the Mammotrophs and gonadotrophs in the anterior pituitary gland of rats with protein-calorie malnutrition.  Am J Anat. 1980;  158 521-531
    CrossrefPubMedGoogle Scholar
  • 24 Chik C L, Ho A K, Brown G M. Effect of food restriction on 24-h serum and pineal melatonin content in male rats.  Acta Endocrinol (Copenh). 1987;  115 507-513
    PubMedGoogle Scholar
  • 25 Dong Q, Bergendahl M, Huhtaniemi I, Handelsmen D J. Effect of undernutrition on pulsatile luteinizing hormone (LH) secretion in castrate and intact male rats using an ultrasensitive immunofluorometric LH assay.  Endocrinol. 1994;  135 (2) 745-750
    CrossrefPubMedGoogle Scholar
  • 26 Wade G N, Lempicki R L, Panicker A K, Frisbee R M, Blaustein J D. Leptin facilitates and inhibits sexual behavior in female hamsters.  Am Physiol Soc. 1997;  272 R1354-R1358
    PubMedGoogle Scholar
  • 27 Dong Q, Rintala H, Handelsman D J. Androgen receptor function during undernutrition.  J Neuroendocrinol. 1994;  6 (4) 397-402
    PubMedGoogle Scholar
  • 28 Fernandez S, Gonzales C, Patterson A M. Oil enriched diets and behavioral parameters in rats’ recovery from early undernutrition.  Physiol and Behav. 1997;  62 (1) 113-119
    PubMedGoogle Scholar
  • 29 Bayne K. Revised Guide for the Care and Use of Laboratory Animals available.  Am Phys Soc Physiol. 1996;  9 (4) 208-211
    PubMedGoogle Scholar
  • 30 Reeves P G, Nielsen F H, Fahey G C. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc Writing Committee on the reformulation of the AIN-76 rodent diet.  J Nut. 1993;  123 1939-1951
    PubMedGoogle Scholar
  • 31 Bradford M M. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding.  Anal Biochem. 1976;  72 248-254
    CrossrefPubMedGoogle Scholar
  • 32 Carey R J, Krost M, Huston J P. The NMDA receptor and cocaine: evidence thet MK-801 can induce behavioral sensitization effects.  Pharmacol Biochem Behav. 1995;  51 901-908
    CrossrefPubMedGoogle Scholar
  • 33 Sokal R R, Rohlf F J. Biometry. 3rd ed. New York; W.H. Freeman 1995: pp. 887
    Google Scholar
  • 34 Rostom de Mello M A, Oliveira Filho R M, Cury L, Valle L BS. Circulating thyroid hormone levels in young pregnant rats and their fetuses: effect of malnutrition.  Ann Nutr Metab. 1989;  33 181-187
    PubMedGoogle Scholar
  • 35 Pine A P, Jessop N S, Oldham J D. Maternal protein reserves and their influence on lactational performance in rats: the effects of dietary protein restriction and stage of lactation on milk composition.  Br J Nutr. 1994;  702 815-830
    PubMedGoogle Scholar
  • 36 Glass A R, Mellitt R, Vigersky R A, Swerdloff R S. Hypoandrogenism and abnormal regulation of gonadotropin secretion in rats fed a low protein diet.  Endocrinol. 1979;  104 (2) 438-442
    PubMedGoogle Scholar
  • 37 Jean-Faucher C, Berger M, Turckheim M, Veyssiere G, Jean C. Effect of preweaning undernutrition on testicular development in male mice.  Int J Androl. 1982;  5 627-635
    PubMedGoogle Scholar
  • 38 Herbert D C. Testicular testosterone concentrations in protein-calorie malnourished rats.  Arch Androl. 1985;  14 45-49
    PubMedGoogle Scholar
  • 39 Bitran D, Hull E M. Pharmacological analysis of male rat sexual behavior.  Neurosci Biobeh Ver. 1987;  11 365-389
    PubMedGoogle Scholar
  • 40 Shan L X, Rodrigues M C, Janne O A. Regulation of androgen receptor protein and mRNA concentrations by androgens in rat ventral prostate and seminal vesicles and in human hepatoma cells.  Mol Endocrinol. 1990;  4 1636-1646
    PubMedGoogle Scholar
  • 41 Wilson J D. Syndromes of androgen resistance.  Biol Reprod. 1992;  46 168-173
    PubMedGoogle Scholar
  • 42 Raynauld J P, Cousse H, Martin P M. Inhibition of type 1 and type 2 5α-reductase activity by free fatty acids, active ingredients of Permixon.  J Steroid Biochem Mol Biol. 2002;  82 233-239
    CrossrefPubMedGoogle Scholar
  • 43 Fisher J S, Millar M R, Majdic G, Saunders P TK, Fraser H M, Sharpe R M. Immunolocalisation of oestrogen receptor-alpha (ERalpha) within the testis and excurrent ducts of the rat and marmoset monkey from perinatal life to adulthood.  J Endocrinol. 1997;  153 485-495
    CrossrefPubMedGoogle Scholar
  • 44 Saunders P, Fisher J, Sharpe R, Millar M. Expression of oestrogen receptor beta (ERβ) occurs in multiple cell types, including some germ cells, in the rat testis.  J Endocrinol. 1998;  156 R13-R17
    CrossrefPubMedGoogle Scholar
  • 45 van Pelt A, de Rooij D, van der Burg B, van der Saag P, Gustafsson J A, Kuiper G. Ontogeny of estrogen receptor-β expression in rat testis.  Endocrinol. 1999;  140 478-483
    CrossrefPubMedGoogle Scholar
  • 46 Eddy E M, Washburn T F, Bunch D O, Goulding E H, Gladen B C, Lubahn D B, Korach K S. Targeted disruption of the estrogen receptor gene in male mice causes alteration of spermatogenesis and infertility.  Endocrinol. 1996;  137 4796-4805
    CrossrefPubMedGoogle Scholar
  • 47 Couse J, Hewitt S, Bunch D, Sar M, Walker V, Davis B, Korach K. Postnatal sex reversal of the ovaries in mice lacking estrogen receptors α and β.  Science. 1999;  286 2328-2331
    CrossrefPubMedGoogle Scholar
  • 48 Robertson K, O’Donnell L, Jones M, Meachem S, Boon W, Fisher C, Graves K, MacLachlan R, Simpson E. Impairment of spermatogenesis in mice lacking a functional aromatase (CYP19) gene.  Proc Natl Acad Sci USA. 1999;  96 7986-7991
    CrossrefPubMedGoogle Scholar
  • 49 Sharpe R. The role of oestrogen in the male.  Trends Endocrinol Metab. 1998;  9 371-377
    PubMedGoogle Scholar
  • 50 Turner K J, Morley M, MacPherson S, Millar M R, Wilson J A, Sharpe R M, Saunders P TK. Modulation of gene expression by androgen and oestrogens in the testis and prostate of the adult rat following androgen withdrawal.  Mol Cell Endocrinol. 2001;  178 73-87
    CrossrefPubMedGoogle Scholar
  • 51 Kumar M, Leo M, Tindall D. Modulation of androgen receptor transcriptional activity by the estrogen receptor.  J Androl. 1994;  15 534-542
    PubMedGoogle Scholar
  • 52 Hall J, McDonnell D. The estrogen receptor β-isoform (ERβ) of the human estrogen receptor modulates ERα transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens.  Endocrinol. 1999;  140 5566-5578
    CrossrefPubMedGoogle Scholar
  • 53 Lee Y F, Shyr C R, Thin T, Lin W J, Chang C. Convergence of two repressors through heterodimer formation of androgen receptor and testicular orphan receptor-4: a unique signaling pathway in the steroid receptor superfamily.  Proc Natl Acad Sci USA. 1999;  96 14 724-14 729
    PubMedGoogle Scholar
  • 54 Jenster G. Coactivators and corepressors as mediators of nuclear receptor function: an update.  Mol Cell Endocrinol. 1998;  143 1-7
    CrossrefPubMedGoogle Scholar

Dra. C. da Fonte Ramos

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