- Biomedical Research (2006) Volume 17, Issue 1
Mini review: Stress and how it affects reproductionAmar Chatterjee1*, Mohd Hamim Rajikin1, Rita Chatterjee1, Sumitabha Ghosh2
- *Corresponding Author:
- Amar Chatterjee
Department of Physiology, Faculty of Medicine
Universiti Teknologi MARA 40450 Shah Alam
E-mail: amar_chatterjee ( at ) hotmail.com
Accepted December 0 9, 2005
Chronic anxiety, depression or physical exertion-associated stress consistently activates the hypothalamic-pituitary-adrenal (HPA) axis. Each individual component of the HPA axis, such as CRH, ACTH, β-endorphin or glucocorticoid exerts deleterious effect on the hypo-thalamic-pituitary-gonadal (HPG) axis and subsequently leads to reproductive failure. Gonadotropin-releasing hormone (GnRH) secretion and the response of gonadotrophs to GnRH stimulation are severely impaired. Moreover, failure of gonadal response to gonad-otropin concurrently results in deficient steroidogenesis, anovulation, defective endometrial decidualization and implantation, abnormal fetal outcome and delayed parturition. In male, a consistent testosterone deficiency due to stress-linked altered functioning of the HPG axis has also been documented. Stress-associated growth hormone (GH) deficiency with a corresponding deficiency of insulin-like growth factor-1 (IGF-1) at the level of the hypothalamus, pituitary, ovary, and uter-ine endometrium leads to defective reproductive outcome and lactation. GH or IGF-1 deficiency also impairs testosterone biosynthesis, spermatogenesis, sperm maturation and erectile process.
Activation of the HPA axis concurrently inhibits HPG axis in stress
Individuals frequently encounter stressful conditions. In vertebrates, a major mechanism of physiological response to stress is hyperactivation of the hypothalamic-pituitary- adrenal (HPA) axis. HPA axis hyperactivation is evident in major depressive [1,2] and anxiety  disorders. The occurrence of persistent increase in serum concentration of glucocorticoid in physical and psychological stress in primates [4,5], rodents  and domestic species  is well documented.
Chronic hyperactivation of glucocorticoids, however, re-sults in the development of diabetes, hypertension and even cancer . The principal regulator of the HPA axis, corticotrophin-releasing hormone (CRH) and its receptors are located in the ovaries, decidual endometrial stroma, placental trophoblast and even in the Leydig cells of the testis [9-12].
Although the inhibitory effect of CRH in decreased LH and FSH secretion , ovarian steroidogenesis  and testosterone biosynthesis  has been documented, yet the locally produced CRH is found to be essential in promoting endometrial decidualization and implantation . CRH may moreover act as the placental clock to trigger the onset of parturition . On the other hand, CRH-activated β-endorphin  or corticotropin (ACTH)  is known to suppress the gonadotropin-releasing hormone (GnRH) pulses [18,20] with a corresponding attenuation of pulsatile release of luteinizing hormone (LH) [21,22] which subsequently leads to anovulation , interruption of endometrial decidualization  and pregnancy wastage .
The essential rhythmic pattern of GnRH secretion from the hypothalamus leads to an increased pulsatile release of LH . Moreover, in concert with follicle stimulating hormone (FSH), LH dictates preovulatory follicular growth and estrogen production which subsequently trig-gers LH surge and ovulation . Daley et al  have shown that stress-like concentration of glucocorticoid blocks estrogen-dependent increase in pituitary tissue concentration of GnRH and GnRH receptor mRNA. Therefore, the concept of glucocorticoid-linked reduced responsiveness of the gonadotrophs to GnRH  with a corresponding attenuation of gonadotropin secretion  seems to be logical. An excess of glucocorticoid has been found to suppress GnRH secretion .
Experimental results of the effectiveness of excessive glucocorticoid on gonadotropin secretion, however, re-main conflicting. When animal studies have linked increased CRH to decreased gonadotropin secretion , human studies using short-term infusion of CRH , conversely presented contradictory data. Since glucocorti-coid receptors have been demonstrated in rat ovaries  and ovarian granulosa cell cytosol , the direct effect of glucocorticoids  could possibly result in follicular atresia  by suppressing the action of LH/hCG at the receptor level . Glucocorticoid-induced suppression of granulosa cell aromatase enzyme activity finally re-sults in estrogen deficiency . Estrogen deficiency has also been recorded in anxiety and depression-related stress .
Investigators have recorded that glucocorticoid could greatly diminish the tissue uptake of estrogen  and estrogen-stimulated synthesis of DNA in the uterus . Moreover, the number of estrogen receptors , blood flow , protein synthesis , prostaglandin synthesis  and insulin-like growth factor-1 (IGF-1) mRNA ex-pression  in the uterus are found to be inhibited by glucocorticoids. Most of these estrogen-induced uterine profiles are essentially important for blastocyst implanta-tion , endometrial decidualization , pregnancy maintenance  and parturition . It is, however, im-portant to note that glucocorticoid receptors in the uterus remain unaltered under the condition of chronic stress or even after prolonged glucocorticoid administration . Estrogen deficiency not only impairs luteal steroidogene-sis in pregnant rats , it also jeopardizes receptor ex-pression of estrogen and progesterone in uteri , which subsequently results in pregnancy wastage  and parturition failure . Moreover, the parental stress-associa-ted shorter gestation, complicated delivery, smaller birth weight in humans [55,56] could possibly be linked to the free access of excess glucocorticoid through placental barrier . Excess glucocorticoid is also found to cause delayed parturition and still birth in rats . Highly anx-ious women have similarly been shown to have a signifi-cant reduction of uterine blood flow in the third trimester of pregnancy, as compared to less anxious women . In rats, chronic stress during pregnancy exerts profound long-term influences on the offspring .
Although females are known to be more vulnerable to stress and exhibits hyperactivity of the HPA axis functisus glucocorticoid is also found to attenuate plasma testosterone concentra-tion in men by inhibiting GnRH secretion [29,63]. The suppressive effect of ACTH on gonadotropin secretion  has been recorded in male patients with Cushing’s syndrome . Moreover, the suppressive effect of ACTH on gonadotropin secretion has never been recorded in patients with adrenocortical insufficiency .
Glucocorticoid receptors have been located in the rat Leydig cells . The restraint stress-induced reduction in plasma concentration of testosterone, however, is claimed to be LH-independent , but appears to be related to the inhibition of the activities of steroidogenic enzymes . β-endorphin blocker, such as naloxone or naltrexone has been shown to counteract the inhibitory effect of restraint stress on plasma testosterone levels by maintaining the normal functioning of the testicular ster-oidogenic enzymes . In stressed rats, a concomitant rise in testicular nitric oxide (NO) concurrently with down regulated testosterone production has also been documented .
HPA axis activation and suppression of the GH-IGF-1 axis
The HPA axis activation and growth hormone (GH) blunting have in fact been linked in a primate study . A blunted GH response to clonidine has however, been experienced in both anxiety and depression . Attenuated release of GH in response to stress has been recognized long ago in experimental animals . Experimental evidences suggest that GH may function as a cogonadotropin . GH receptor mRNA expression and GH binding protein (GHBP) have been detected in the ovary of humans  and in several animal species [77-79]. A number of in vitro studies have shown that GH can influence oocyte maturation, increase receptors to gonad-otropin, thereby aiding folliculogenesis .
It is known that sexual maturation is delayed in Laron dwarfism  and growth hormone insensitivity also impairs the ability of young adult female mice to form functional corpora lutea of pregnancy . However, a full
Stress and reproduction
reproductive potential requires actions of GH and adequ-ate levels of insulin-like growth factor-1 (IGF-1) in peripheral circulation . Therefore, to induce ovulation in Laron dwarfism, IGF-1 treatment is often preferred . GH-receptor gene knockout mice are found to be IGF-1 deficient . IGF-1 receptors were detected in the pituitary, gonads and reproductive tract  and the influence of IGF-1 on the release of GnRH  and gonadotropin , follicular steroidogenesis, ovarian follicular growth, and ovulation [see 88] have also been documented.
IGF-1 mRNA was identified in the adult testis . In the human testis, IGF-1 was also identified in Leydig cells, Sertoli cells and primary spermatocytes . A vital role of IGF-1 in testicular steroidogenesis  has also been suggested. GH treatment to adult GH/IGF-1-deficient Ames dwarf mice increased plasma IGF-1 level and concurrently increased androstenedione and testosterone release from the isolated testes . In hypophysectomized rats, GH administration resulted in an increase in the LH receptor content of the testis  and GH has been shown to enhance the testicular responsiveness to gonadotropin treatment .
Although, an enormous amount of experimental and clini-cal data are available, the absolute pathway between the stress-induced hyperactivation of the HPA axis and corresponding attenuation of the HPG axis has yet to be deter-mined
The encouraging cooperation of Dato’ Professor Khalid Yusoff (Dean) and Dato’ Professor Khairul Anuar Abdul-lah (Deputy Dean, Academic), Faculty of Medicine, Uni-versiti Teknologi MARA, is highly appreciated.
- Bjorntorp P. Behavior and metabolic disease. Int J Behav Med 1996; 3: 285-302.
- Chrousos GP, Gold PW. The concept of stress and stress system disorders. Overview of physical and be-havioral homeostasis. JAMA 1992; 267: 1244-1252.
- Chrousos GP et al. Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. Ann Intern Med 1998; 129: 229-240.
- Darrell WB et al. Corticosteroid regulation of gonado-tropin and prolactin secretion in the rat. Endocrinology 1990; 126: 159-166.
- Norman RL et al. Restraint inhibits luteinizing hor-mone secretion in the follicular phase of the menstrual cycle in rhesus macaques. Biol Reprod 1994; 50: 16-26.
- Suzuki S et al. Pituitary-dependent and independent secretion of CS caused by bacterial endotoxin in rats. Am J Physiol 1986; 250: E470-E 474.
- Guillaume V et al. Effect of chronic active immunization anti-corticotropin- relasing factor on the pituitary-adrenal function in the sheep. Endocrinology 1992; 130: 2291-2298.
- McEwen BS. Stress adaptation and disease. Allostasis and allostatic load. N Y Acad Sci 1998; 840: 33-44.
- Mastorakos et al Immunoreactive corticotrophin-releasing hormone and its binding Sites in the rat ovary. J Clin Invest 1993; 92: 961-968.
- Mastorakos G et al. Presence of immunoreactive corticotrophin-releasing hormone in human endometrium. J Clin Endocrinol Metab 1996; 81: 1046-1050.
- Petraglia F et al. Human decidua and in vitro decidualized endometrial stromal cells at term contain immunoreactive corticotropin-releasing factor (CRF) and CRF-messenger ribonucleic acid. J Clin Endocrinol Metab 1992; 74: 1427-1431.
- Makrigiannakis A et al. Corticotropin-releasing hormone (CRH) is expressed at the implantation sites of early pregnant rat uterus. Life Sci 1995; 57: 1869-1875.
- Deborah HO, Michel F. Corticotropin-releasing hor-mone inhibits gonadotropin secretion in the ovariectomized rhesus monkey. J Clin Endocrinol Metab 1987; 65: 262-267.
- Ghizzoni L et al. Corticotropin-releasing hormone (CRH) inhibits steroid biosynthesis by cultured human granulosalutein cells in a CRH and interleukin-1 receptor mediated fashion. Endocrinology 1997; 130: 4806-4811.
- Fabri A et al. Corticotropin-releasing factor is produced by the rat Leydig cells and has a major local antireproductive role in the testis. Endocrinology 1990; 127: 1541-1543.
- Zoumakis E et al. Cycle and age related changes in corticotrophin-releasing hormone Level in human endometrium and ovaries. Gynecol Endocrinol 2001; 15: 98-102.
- Challis JRG et al. Endocrine and paracrine regulation of birth at term and preterm. Endocr Rev 2000; 21: 514 -550.
- Chen MD et al. Hypothalamic “stress” and gonadotro-pin-releasing pulse generatoractivity in the rhesus monkey: role of the ovary. Neuroendocrinology 1992; 56: 666-673.
- Plotsky PM. Pathways to the secretion of adrenocorti-cotropin- a view from the portal. J Neuroendocrinol 1991; 3: 1-9.
- Morley JE. The endocrinology of the opiate and opioid peptides. Metabolism 1981; 30: 195-209.
- Schulz R et al. β-endorphin and dynorphine control serum luteinizing hormone level in Immature female rats. Nature 1981; 294: 757.
- Kinoshita F et al. Effect of β-endorphin on pulsatile luteinizing hormone release in conscious castrated rats. Life Sci 1980; 27: 843-848.
- Chatterjee A et al. Acute physical activity and its impact on ovulation in rats.Biomed Res 1994; 5: 57-60.
- Chatterjee A et al. Treadmill running modulates endo-metrial decidualization in rats. Biomed Res 1995; 6: 109-113.
- Chatterjee A, Harper MJK. Interruption of implantation and gestation in rats by reserpine, chlorpromazine and ACTH: possible mode of action. Endocrinology 1970; 87: 966-969.
- Moenter SM et al. The estradiol-induced surge of gonadotropin-releasing hormone in the ewe. Endocrinol-ogy 1990; 127; 1375-1384.
- McNeilly AS et al. Gonadotrophic control of follicle growth in the ewe. J Reprod Fertil 1991; 92: 177-186.
- Daley CA et al. Effect of stress-like concentration of cortisol on the feedback potency of estradiol in orchid-dectomized sheep. Anim Reprod Sci 2000; 59: 167- 178.
- Sakakura N et al. Inhibition of luteinizing hormone secretion induced by synthetic LRH By long-term treatment with glucocorticoids in human subjects. J Clin Endocrinol Metab 1975; 40: 774-779.
- Fonda et al. The effect of adrenocorticotropin or hydrocortisone on serum luteinizing hormone concentrations after adrenalectomy and/or ovariectomy in the prepube-rtal girls. Endocrinology 1984; 114: 268-273.
- Dubey AK, Plant TM. A suppression of gonadotropin secretion by cortisol in castrated rhesus monkeys (Macaca mulatta) mediated by the interruption of hypothalamic gonadotropin-releasing hormone. Biol Rep-rod 1985; 33: 423-431.
- Olster DH, Ferin M. Corticotropin-releasing hormone inhibits gonadotropin secretion in the ovariectomized rhesus monkey. J Clin Endocrinol Metab 1987; 65: 262 -267.
- Thomas MA et al. Dose-response effects of exogenous pulsatile human corticotrophin-releasing hormone on adrenocorticotropin, cortisol and gonadotropin concen-trations in agonadal women. J Clin Endocrinol Metab 1991; 72: 1249-1254.
- Shreiber JR et al. Rat ovary glucocorticoid receptor: identification and characterization. Steroids 1982; 39: 569-584.
- Louvet JP et al. Glucocorticoid receptors in rat ovarian granulose cell cytosol.59th Annual Meeting of The Endocrine Society, Chicago IL, 1977; p 601 (Abstract).
- Meurer KA et al. Decreased follicular steroids and insulin-like growth factor-1 and increased atresia in diabetic gilts during follicular growth stimulated with PMSG. J Reprod Fert 1991; 91: 187-196.
- Schoonmaker JN, Erickson GF. Glucocorticoid modu-lation of follicle- stimulating hormone-mediated granulosa cell differentiation. Endocrinology 1983; 1356- 1363.
- Hsueh AJW, Erickson GF. Glucocorticoid inhibition of FSH-mediated estrogen production of cultured rat granulose cells. Steroids 1983; 32: 639- 643.
- Andrade TG et al. Anxiolytic effect of estradiol in the median raphe nucleus mediated by 5-HT1A receptors. Behav Brain Res 2005; 163: 18-25.
- Campbell PS. The mechanism of the inhibition of uterotropic responses by acute dexamethasone pretreat-ment. Endocrinology 1978; 103: 716-723.
- Bigsby RM. Progesterone and dexamethasone inhibition of estrogen-induced synthesis of DNA and com-plement in rat uterine epithelium: effects of antiproges-terone compounds. J Steroid Biochem Mol Biol 1993; 45: 295-301.
- Zamorano P et al. Effects of 5 alpha-dihydrotestosterone and dexamethasone on estrogen receptors of the anterior pituitary and uterus. Steroids 1992; 57: 18-26.
- Monheit AG, Resnik R. Corticoid suppression of estro-gen-induced uterine blood flow in nonpregnant sheep. Am J Obstet Gynecol 1981; 139: 454-458.
- Sullivan DA et al. Steroid hormone regulation of free secretory component in the rat uterus. Immunology 1983; 49: 379-386.
- Jacobs AL et al. Regulated expression of prostaglandin endoperoxide synthase-2 by uterine stroma. Endocri-nology 1994; 135: 1807-1815.
- Sahlin L. Dexamethasone attenuates the estradiol-induced increase of IGF-1 mRNA in the rat uterus. J Steroid Biochem Mol Biol 1995; 55: 9-15.
- Psychoyos A. Endocrine control of egg implantation. In: Greep RO, Astwood EG, Greiger SR (eds.) Hand Book of Physiology Vol II, part 2. American Physio- logical Society, Washington DC 1973; 187-215.
- Chatterjee et al. Dexamethasone modulation of endo-metrial decidualization in rats. Biomed Res 1995; 6: 153-156.
- Chatterjee A. The possible mode of action of prostaglandins: VII. Evidence of antifertility effect of prostaglandin E1 in rats. Prostaglandins 1974; 6: 413-416.
- Chatterjee A et al. Dexamethasone modulation of gestation length and parturition in rats. Pharmacol Res 1993; 27: 359-364.
- Gunin AG. Effect of long-term glucocorticoid treatment on estradiol-induced proliferation in the uterus of ovariectomized rats. J Endocrinol 1998; 157: 481- 488.
- Shetty et al. Bockade of estrogen synthesis with an aromatase inhibitor affects luteal function of the pseudopregnant rat. J Steroid Biochem Mol Biol 1995; 55: 347-353.
- Bergman et al. Upregulation of uterine oestrogen receptor and its messenger ribonucleic acid during the mouse oestrous cycle: The role of oestradiol. Endocrinology 1992; 130: 1923-1930.
- Sulaiman SA et al. Indigenous herbal formulation and its contraceptive profile in rats. Biomed Res 2001; 12: 65-69.
- Hedegaard M et al. Do stressful life events affect duration of gestation and risk of preterm delivery? Epide-miology 1996; 7: 339-345.
- da Costa D et al. Psychological predictors of labor/ delivery and infant birth weight: a prospective multivariate study. J Psychosom Obstet Gynecol 2000; 21: 137-148.
- Gitau R et al. Fetal exposure to maternal cortisol. The Lancet 1998; 352: 707-708.
- Teixeira JM et al Association between maternal anxiety in pregnancy and increased uterine artery resistance index: cohort based study. BMJ 1999; 318: 153-157.
- Maccari S et al. Prenatal stress and long-term consequences: implications of glucocorticoid hormones. Neurosci Biobehav Rev 2003; 27: 119-127.
- Kennett GA et al. Female rats are more vulnerable than males in an animal model of depression: the possible role of serotonin. Brain Res 1986; 382: 416-421.
- Weinstock M et al. Gender differences in sympathoad-renal activity in rats at rest and in response to footshock stress. Int J Dev Neurosci 1998; 16: 289- 295.
- Lopez-Calderon A et al. Stress-induced changes in testis function. J Steroid Biochem Mol Biol 1991; 40: 473 -479.
- Vierhapper H. LH-RH stimulated LH secretion in hu-man endocrine disease. Acta Endocrinol 1985; 109: 1- 25.
- Vierhapper H et al. Suppression of luteinizing hormone induced by adrenocorticotropin in healthy women. J Endocrinol 1981; 91: 399-403.
- Luton J-P et al. Reversible gonadotropin deficiency in male Cushing’s disease. J Clin Endocrinol Metab 1977; 45: 488-495.
- Vierhapper H et al. Gonadotropin secretion in adreno-cortical insufficiency: Impact of glucocorticoid substit-ution. Acta Endocrinol 1982; 101: 580-585.
- Stalker A et al. Covalent affinity labeling radioautography, and immunocytochemistry localized the gluco-corticoid receptor in rat testicular Leydig cells. Am J Anat 1989; 386: 369-377.
- Orr TE, Mann DR. Effect of restraint stress on plasma LH and testosterone concentrations, Leydig cell LH/ hCG receptors, and in vitro testicular steroidogenesis in adult rats. Horm Behav 1990; 24: 324-341.
- Hales DB, Payne AH. Glucocorticoid-mediated repression of P450scc mRNA and de novo synthesis in cul-tured Leydig cells. Endocrinology 1989; 124: 2099- 2104.
- Kostic T et al. The effect of opioid antagonists in local regulation of testicular response to acute stress in adult rats. Steroids 1997; 62: 703-708.
- Tatjana S et al. Inhibitory effects of stress-activated nitric oxide on antioxidant enzymes and testicular steroidogenesis. J Steroid Biochem Mol Biol 2000; 75: 299 -306.
- Coplan et al. Growth hormone response to clonidine in adversely reared young adult primates: relationship to serial cerebrospinal fluid corticotropin-releasing factor concentrations. Psychiatry Res 2000; 95: 93-102.
- Uhde TW et al. Blunted growth hormone response to clonidine in panic disorder patients. Biol Psychiatry 1986; 21: 1081-1085.
- Campbell GA et al. Effects of starvation in rats on serum levels of follicle stimulating hormone, luteinizing hormone, thyrotropin, growth hormone and prolac-tin; response to LH-releasing hormone and thyrotropin-releasing hormone. Endocrinology 1977; 100: 580-587.
- Childs GV et al. Cells that express luteinizing hormone (LH) and follicle- stimulating hormone (FSH) beta-subunit messenger ribonucleic acids during the estrous cycle: the major contributors contain LH beta, FSH beta and/or growth hormone. Endocrinology 1994; 134: 990-997.
- Sharara FI, Nieman LK. Identification and cellular localization of growth hormone receptor gene expres-sion in the human ovary. J Clin Endocrinol Metab 1994; 79: 670-672.
- Lobie PE et al. Cellular localization of the growth hormone receptor/binding protein in the male and female reproductive systems. Endocrinology 1990; 126:2214- 2221.
- Yuan W, Lucy MC. Messenger ribonucleic acid ex-pression for growth hormone receptor, luteinizing hormone receptor and steroidogenic enzymes during the estrous cycle and pregnancy in porcine and bovine corpora lutea. Domest Anim Endocrinol 1996; 13: 431-444.
- Sakaguchi K et al. Tissue-specific regulation of growth hormone receptor and growth hormone binding protein gene expression during pregnancy and lactation in the rat. Endocr J 1998; 45: S105-107.
- Sirotkin AV, Makarevich AV. Growth hormone can regulate functions of porcine ovarian Granulose cells through the cAMP/protein kinase A system. Anim Reprod Sci 2002; 70: 111-126.
- Laron Z. Growth hormone insensitivity (Laron syndrome). Rev Endocr Metab Disord 2002; 3: 347-355.
- Zaczek D et al. Impact of growth hormone resistance on female reproductive function. New insights from growth hormone receptor knockout mice. Biol Reprod 2002; 67: 1115-1124.
- Chandrashekar et al. Pituitary and testicular function in growth hormone receptor gene knockout mice. Endocrinology 1999; 140: 1082-1088.
- Ibrahim ZHZ et al. The use of biosynthetic human growth hormone to augment ovulation induction with buserelin acetate human menopausal gonadotrophin treatment in women with a poor ovarian response. Fer-til Steril 1991; 55: 204- 204.
- Chandrashekar et al. Testicular endocrine function in growth hormone receptor gene disrupted mice. Endo-crinology 2001; 142: 3443-3450.
- Codner E, Cassorla F. Growth hormone and reproduc-tive function. Mol Cell Endocrinol 2002; 186: 133- 136.
- Lackey BR et al. The insulin-like growth factor (IGF) system and gonadotropin regulation: actions and interactions. Cytokine Growth Factor Rev 1999; 10: 201- 217.
- Mazerbourg S et al. The insulin-like growth factor system: a key determinant role in the growth and selection of ovarian follicles. A comparative species study. Re- prod Domest Anim 2003; 38: 247-258.
- Lin T et al. Regulation of insulin-like growth factor-1 messenger ribonucleic acid expression in Leydig cells. Mol Cell Endocrinol 1990; 73: 147-152.
- Vannelli BG et al. Insulin-like growth factor-1 (IGF-1) and IGF-! Receptor in human testis: am immunohisto-chemical study. Fertil Steril 1988; 49: 666-669.
- Kasson BG, Hsueh AJ. Insulin-like growth factor-1 augments gonadotropin- stimulated androgen biosynthesis by cultured rat testicular cells. Mol Cell Endocrinol 1987; 52: 27-34.
- Chandrashekar V, Bartke A. Induction of endogenous insulin-like growth factor-1 secretion alters the hypothalamic-pituitary-testicular function in growth hormone deficient adult dwarf mice. Biol Reprod 1993; 48: 544-551.
- Zipf WB et al Prolactin, growth hormone and luteiniz-ing hormone in the maintenance of testicular luteinizing hormone receptor. Endocrinology 1978; 103: 595- 600.
- Swerdloff RS, Odell WD. Modulating influence of FSH, GH and prolactin on LH-stimulated testosterone secretion. In: Troen P, Nankin HR (eds.), The Testis in Normal and Infertile Men. New York: Raven Press; 1977; 395-401.