**9. References**

128 Sex Steroids

of these authors (e.g. [112-114]) also implicates a regulatory role for testosterone on the autonomic nervous system and, possibly, the sympatho-adrenal medullary system. Further

Lactation is a physiological state that can have profound effects on both the basal and stressinduced activity of the hypothalamo-pituitary adrenal axis. In many species, including humans, ungulates and rodents, it has been consistently found that lactating females show attenuated neuroendocrine responses to stress (for reviews see [115-117]) and anxietyrelated behaviours (for reviews see [116, 118, 119]). The alterations in the hypothalamopituitary adrenal axis that result in reduced responses to stress begin to emerge in late pregnancy and occur in a continuum throughout lactation (for reviews see [116, 118, 120, 121]). Although the mechanisms for attenuated hypothalamo-pituitary adrenal axis responses to stress during lactation are not fully known, it appears that they include reduced synthesis and secretion of CRH and AVP due to enhanced negative feedback by glucocorticoids and/or reduced noradrenergic stimulatory input from the brain stem, reduced pituitary responsiveness to CRH and AVP and, possibly, inhibition by oxytocin and prolactin [1]. We have shown in sheep that the greatest attenuation of the hypothalamopituitary adrenal axis is achieved when the lactating mother is suckled [122] and this is likely to also be the case for humans when breastfeeding [1]. Despite the many published reports of attenuated stress responses in lactating females this has not always been the case and the nature of the stressor seems to be important. It has been shown in both sheep [123] and humans [87] that the there is activation of the hypothalamo-pituitary adrenal axis in response to a stressor that may threaten the welfare of the infant by virtue of harming the mother. This makes perfect sense given that the mother would require a stress response in order to dispose of the threat posed to herself and her offspring. This underscores the importance of being able to mount stress responses so that homeostasis can be restored

Although there are various ways to define stress there is generally acceptance that stress responses occur in response to noxious stimuli, whether perceived or real, commonly called stressors. A range of physiological systems are activated with the two of the most prominent being the sympatho-adrenal medullary system and the hypothalamo-pituitary adrenal axis. The catecholamines and glucocorticoids, released by each system respectively, have farreaching effects within the body to re-establish the homeostasis that was disrupted by stressors. Such stress responses are vital for a healthy life. Nevertheless, when the stress systems are frequently or continually activated, the on-going action of the catecholamines and glucocorticoids can be destructive and lead to pathological conditions. An inability to mount an appropriate stress response may also result in illness. Therefore, it follows that understanding stress responses, and the factors that affect stress responses, is paramount to develop strategies and treatments to avoid or cure stress-induced disorders and pathologies. These factors include sex, sex steroids and physiological state, particularly reproductive state. There are differences between males and females in various illnesses and pathological states and many of these are those induced or exacerbated by frequent or chronic stress. Males and females respond differently to some stressors and not others. The implications for health and survival of these different stress responses are unknown and research is required to determine this. At least some of the mechanisms for sex differences in stress responses are

research is necessary to confirm this and the research needs to be extended to males.

(Section 1).

**7. Conclusions** 


Sex Differences and the Role of Sex Steroids in Sympatho-Adrenal

Metabolism, 1988. 66(4): p. 722-726.

York. p. 20-36.

335(20): p. 1480-5.

25(1): p. 1-35.

p. 493-500.

278(4): p. H1269-73.

*glucocorticoids.* Endocrinology, 1985. 116: p. 2273-2278.

*social stress.* Endocrinology, 1987. 121(5): p. 1605-1610.

*from 3 populations.* Hypertension, 2000. 35(6): p. 1301-6.

*person-years.* Int J Epidemiol, 2005. 34(3): p. 655-63.

*and stress.* J.Psychosom.Res., 2002. 53(4): p. 865-871.

*disease states.* Psychosom Med, 2003. 65(1): p. 46-62.

Nat Rev Drug Discov, 2005. 4(2): p. 165-71.

*hippocampal astrocytes.* Neuroendocrinology., 1993. 57: p. 7-13.

*during behavioral stress.* Psychophysiology, 1990. 27(2): p. 125-135.

Medullary System and Hypothalamo-Pituitary Adrenal Axis Responses to Stress 131

[29] Sapolsky, R.M., *Stress-induced suppression of testicular function in the wild baboon: Role of* 

[30] Sapolsky, R.M. and L.C. Krey, *Stress-induced suppression of luteinizing hormone* 

[31] Sapolsky, R.M. and G.E. Mott, *Social subordinance in wild baboons is associated with* 

[32] Sapolsky, R.M., *Glands, Gooseflesh and Hormones*, in *Why zebra's don't get ulcers: a guide to* 

[33] Tombaugh, G.C. and R.M. Sapolsky, *Endocrine features of glucocorticoid endangerment in* 

[34] Stoney, C.M., et al., *Influences of the normal menstrual cycle on physiologic functioning* 

[35] Schobel, H.P., et al., *Preeclampsia -- a state of sympathetic overactivity.* N Engl J Med, 1996.

[36] Phillips, D.I., et al., *Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome?* J Clin Endocrinol Metab, 1998. 83(3): p. 757-60. [37] Phillips, D.I., et al., *Low birth weight predicts elevated plasma cortisol concentrations in adults* 

[38] Heim, C., U. Ehlert, and D.H. Hellhammer, *The potential role of hypocortisolism in the* 

[39] Yang, C.C., et al., *Preeclamptic pregnancy is associated with increased sympathetic and* 

[40] Kajantie, E., et al., *Placental 11 beta-hydroxysteroid dehydrogenase-2 and fetal* 

[41] Kajantie, E., et al., *Pre-eclampsia is associated with increased risk of stroke in the adult offspring: the Helsinki birth cohort study.* Stroke, 2009. 40(4): p. 1176-80. [42] Kajantie, E., et al., *Size at birth as a predictor of mortality in adulthood: a follow-up of 350 000* 

[43] Tsigos, C. and G.P. Chrousos, *Hypothalamic-pituitary-adrenal axis, neuroendocrine factors* 

[44] Treiber, F.A., et al., *Cardiovascular reactivity and development of preclinical and clinical* 

[45] Kreier, F., et al., *Hypothesis: shifting the equilibrium from activity to food leads to autonomic unbalance and the metabolic syndrome.* Diabetes, 2003. 52(11): p. 2652-6. [46] Schwartz, A.R., et al., *Toward a causal model of cardiovascular responses to stress and the development of cardiovascular disease.* Psychosom Med, 2003. 65(1): p. 22-35. [47] Brown, E.S., F.P. Varghese, and B.S. McEwen, *Association of depression with medical* 

[48] Licinio, J. and M.L. Wong, *Depression, antidepressants and suicidality: a critical appraisal.*

*illness: does cortisol play a role?* Biol Psychiatry, 2004. 55(1): p. 1-9.

*pathophysiology of stress-related bodily disorders.* Psychoneuroendocrinology, 2000.

*decreased parasympathetic control of HR.* Am J Physiol Heart Circ Physiol, 2000.

*cortisol/cortisone shuttle in small preterm infants.* J Clin Endocrinol Metab, 2003. 88(1):

*concentrations in wild baboons: role of opiates.* Journal of Clinical Endocrinology &

*suppressed high density lipoprotein-cholesterol concentrations: the possible role of chronic* 

*stress, stress-related diseases and coping*. 1994, W.H. Freeman and Company: New


[11] Antoni, F.A., *Vasopressinergic control of pituitary adrenocorticotropin secretion comes of age.*

[12] Delitala, G. and M. Motta, *Opioid peptides and pituitary function Basic and clinical aspects,* 

[13] Duclos, M., et al., *Corticosterone-dependent metabolic and neuroendocrine abnormalities in* 

[14] Engler, D., et al., *Corticotropin-release inhibitory factor Evidence for dual stimulatory and* 

[15] Bohus, B., et al., *Neuroendocrine states and behavioral and physiological stress responses.*

[16] Rivier, C. and S. Rivest, *Effect of stress on the activity of the hypothalamic-pituitary- gonadal* 

[17] Chrousos, G.P., *The HPA axis and the stress response.* Endocrine Research, 2000. 26(4): p.

[18] Chrousos, G.P., *Stress, chronic inflammation, and emotional and physical well-being:* 

[19] Chrousos, G.P., *The role of stress and the hypothalamic-pituitary-adrenal axis in the* 

[20] Chrousos, G.P., *Stress and disorders of the stress system.* Nature Reviews Endocrinology,

[21] Chrousos, G.P., *Regulation and dysregulation of the hypothalamic-pituitary-adrenal axis. The* 

[22] Chrousos, G.P., *Stressors, stress, and neuroendocrine integration of the adaptive response. The* 

[23] Chrousos, G.P., *The role of stress and the hypothalamic-pituitary-adrenal axis in the* 

[24] Sapolsky, R.M., L.M. Romero, and A.U. Munck, *How do glucocorticoids influence stress* 

[25] Miller, A.H., et al., *Adrenal steroid receptor activation in rat brain and pituitary following* 

[26] Reul, J.M. and E.R. de Kloet, *Two receptor systems for corticosterone in rat brain:* 

[27] de Kloet, E.R., N.Y. Rots, and A.R. Cools, *Brain-corticosteroid hormone dialogue: slow and* 

[28] Kim, P.J., et al., *Evaluation of RU28318 and RU40555 as selective mineralocorticoid receptor* 

Int.J.Obes.Relat Metab Disord., 2000. 24 Suppl 2: p. S50-S55.

*[Review].* Endocrine Reviews, 2000. 21(1): p. 55-89.

*persistent.* Cell Mol.Neurobiol., 1996. 16(3): p. 345-356.

*studies.* J.Steroid Biochem.Mol.Biol., 1998. 67(3): p. 213-222.

*obese Zucker rats in relation to feeding.* Am.J.Physiol Endocrinol.Metab, 2005. 288(1):

*inhibitory hypothalamic regulation over adrenocorticotropin secretion and biosynthesis.*

*axis: peripheral and central mechanisms.* Biology of Reproduction, 1991. 45: p. 523-532.

*concurrent effects and chronic sequelae.* J.Allergy Clin.Immunol., 2000. 106(5 Suppl): p.

*pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes.*

*corticotropin-releasing hormone perspective.* Endocrinol.Metab Clin.North Am., 1992.

*1997 Hans Selye Memorial Lecture.* Annals.of the.New York.Academy.of Sciences.,

*pathogenesis of the metabolic syndrome: neuro-endocrine and target tissue-related causes.*

*responses? Integrating permissive, suppressive, stimulatory, and preparative actions* 

*dexamethasone: implications for the dexamethasone suppression test.* Biol.Psychiatry,

*microdistribution and differential occupation.* Endocrinology, 1985. 117(6): p. 2505-2511.

*and glucocorticoid receptor antagonists, respectively: receptor measures and functional* 

*in Brain Endocrinology.* 1991, Ravenh Press: New York. p. 217-244.

Trends in Endocrinology and Metabolism, 1994. 5: p. 2-13.

International Journal of Obesity, 2000. 24: p. S50-S55.

Frontiers in Neuroendocrinology, 1993. 14: p. 76-122.

p. E254-E266.

513-514.

S275-S291.

2009. 5(7): p. 374-381.

1998. 851: p. 311-335.

1992. 32(10): p. 850-869.

21(4): p. 833-858.

Prog.Brain Res., 1987. 72: p. 57-70.


Sex Differences and the Role of Sex Steroids in Sympatho-Adrenal

Biochem Behav, 2007. 86(2): p. 220-33.

Brain Res, 2008. 187(2): p. 228-38.

5(2): p. 105-113.

34(6): p. 381-6.

*comparison.* Neuroscience, 2005. 132(3): p. 755-766.

Medullary System and Hypothalamo-Pituitary Adrenal Axis Responses to Stress 133

[66] Rivalland, E.T.A., et al., *Co-localization and distribution of corticotrophin-releasing hormone,* 

[67] Maestripieri, D., et al., *Between- and within-sex variation in hormonal responses to psychological stress in a large sample of college students.* Stress, 2010. 13(5): p. 413-24. [68] McCormick, C.M. and I.Z. Mathews, *HPA function in adolescence: role of sex hormones in* 

[69] McCormick, C.M., C. Smith, and I.Z. Mathews, *Effects of chronic social stress in adolescence* 

[70] Tilbrook, A.J., A.I. Turner, and I.J. Clarke, *Effects of stress on reproduction in non-rodent* 

[71] Tilbrook, A.J., A.I. Turner, and I.J. Clarke, *Stress and reproduction: central mechanisms and* 

[72] Turner, A.I., P.H. Hemsworth, and A.J. Tilbrook, *Susceptibility of reproduction in female* 

[73] Turner, A.I. and A.J. Tilbrook, *Stress, cortisol and reproduction in female pigs.* Society Of

[74] Breen, K.M. and F.J. Karsch, *New insights regarding glucocorticoids, stress and gonadotropin* 

[75] Moberg, G.P., *Influence of the adrenal axis upon the gonads.* Oxford Reviews of

[76] Crowley, W.R., *Effects of ovarian hormones on norepinephrine and dopamine turnover in* 

[77] Deecher, D.C., et al., *Alleviation of thermoregulatory dysfunction with the new serotonin and* 

[78] Etgen, A.M., M.A. Ansonoff, and A. Quesada, *Mechanisms of ovarian steroid regulation of* 

[79] Renner, K.J., D.L. Allen, and V.N. Luine, *Monoamine levels and turnover in brain: relationship to priming actions of estrogen.* Brain Res Bull, 1986. 16(4): p. 469-75. [80] Weiland, N.G. and P.M. Wise, *Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions.* Endocrinology, 1987. 121(5): p. 1751-8. [81] Alfinito, P.D., et al., *Estradiol increases catecholamine levels in the hypothalamus of ovariectomized rats during the dark-phase.* Eur J Pharmacol, 2009. 616(1-3): p. 334-9. [82] Curtis, A.L., T. Bethea, and R.J. Valentino, *Sexually dimorphic responses of the brain* 

[83] Yanagihara, N., et al., *Stimulation of catecholamine synthesis through unique estrogen* 

*female reproductive physiology.* Horm Behav, 2001. 40(2): p. 169-77.

*individual hypothalamic and extrahypothalamic nuclei.* Neuroendocrinology, 1982.

*norepinephrine reuptake inhibitor desvenlafaxine succinate in ovariectomized rodent* 

*norepinephrine receptor-mediated signal transduction in the hypothalamus: implications for* 

*norepinephrine system to stress and corticotropin-releasing factor.*

*receptors in the bovine adrenomedullary plasma membrane by 17beta-estradiol.* Biochem

*sex differences in non-rodent species.* Stress, 2002. 5: p. 83-100.

Reproduction Fertility and Development, 2002. 14(6): p. 377-391.

Reproduction And Fertility Supplement, 2006. 62: p. 191-203.

*suppression.* Front Neuroendocrinol, 2006. 27(2): p. 233-45.

Reproductive Biology, 1987. 9: p. 456-496.

*models.* Endocrinology, 2007. 148(3): p. 1376-83.

Neuropsychopharmacology, 2006. 31(3): p. 544-54.

Biophys Res Commun, 2006. 339(2): p. 548-53.

*arginine vasopressin and enkephalin in the paraventricular nucleus of sheep: A sex* 

*its regulation and the enduring consequences of exposure to stressors.* Pharmacol

*on anxiety and neuroendocrine response to mild stress in male and female rats.* Behav

*mammals: the role of glucocorticoids and sex differences.* Reviews of Reproduction, 2000.

*pigs to impairment by stress and the role of the hypothalamo-pituitary-adrenal axis.*


[49] Kajantie, E. and D.I. Phillips, *The effects of sex and hormonal status on the physiological* 

[50] Herman, J.P., et al., *Central mechanisms of stress integration: hierarchical circuitry controlling* 

[51] Klein, S.L., *The effects of hormones on sex differences in infection: from genes to behavior.*

[52] Pilote, L., et al., *A comprehensive view of sex-specific issues related to cardiovascular disease.*

[53] Tunstall-Pedoe, H., et al., *Contribution of trends in survival and coronary-event rates to* 

[54] Bekker, M.H.J. and J. van Mens-Verhulst, *Anxiety disorders: Sex differences in prevalence,* 

[55] Breslau, N., H. Chilcoat, and L.R. Schultz, *Anxiety disorders and the emergence of sex* 

[56] Earls, F., *SEX-DIFFERENCES IN PSYCHIATRIC-DISORDERS - ORIGINS AND DEVELOPMENTAL INFLUENCES.* Psychiatric Developments, 1987. 5(1): p. 1-23. [57] Beeson, P.B., *Age and sex associations of 40 autoimmune diseases.* Am J Med, 1994. 96(5): p.

[58] Stackpole, C.A., et al., *Seasonal differences in the effect of isolation and restraint stress on the* 

[59] Tersman, Z., A. Collins, and P. Eneroth, *Cardiovascular responses to psychological and* 

[60] Kudielka, B.M., et al., *Differential heart rate reactivity and recovery after psychosocial stress* 

*gender.* International Journal of Behavioral Medicine, 2004. 11(2): p. 116-121. [61] Turner, A.I., et al., *Influence of sex and gonadal status of sheep on cortisol secretion in response* 

[62] Turner, A.I., et al., *Noradrenaline, but not neuropeptide Y, is elevated in cerebrospinal fluid* 

[63] Turner, A.I., et al., *Stressor specificity of sex differences in hypothalamo-pituitary-adrenal axis* 

*gonadectomized male and female sheep.* Endocrinology, 2010. 151(9): p. 4324-31. [64] Turner, A.I., et al., *A sex difference in the cortisol response to tail docking and ACTH develops* 

[65] Canny, B.J., et al., *Influence of sex and gonadal status on the hypothalamo-pituitary-adrenal* 

*stressors.* Journal of Endocrinology, 2002. 173: p. 113-121.

*ewes.* Neuroendocrinology, 2002. 76: p. 373-380.

*luteinizing hormone response to gonadotropin-releasing hormone in hypothalamopituitary disconnected, gonadectomized rams and ewes.* Biology of Reproduction, 2003. 69: p.

*physiological stressors during the menstrual cycle.* Psychosom.Med., 1991. 53(2): p. 185-

*(TSST) in healthy children, younger adults, and elderly adults: The impact of age and* 

*to ACTH and on cortisol and LH secretion in response to stress: importance of different* 

*from the third cerebral ventricle following audiovisual stress in gonadectomised rams and* 

*activity: cortisol responses to exercise, endotoxin, wetting, and isolation/restraint stress in* 

*between 1 and 8 weeks of age in lambs.* Journal of Endocrinology, 2006. 188(3): p. 443-

*(HPA) axis of the sheep.* Proceedings of the International Congress on Endocrinology,

*differences in major depression.* J Gend Specif Med, 1998. 1(3): p. 33-9.

Canadian Medical Association Journal, 2007. 176(6): p. S1-S44.

*Project populations.* Lancet, 1999. 353(9164): p. 1547-1557.

Neurosci Biobehav Rev, 2000. 24(6): p. 627-38.

78.

24(3): p. 151-180.

S178-S193.

457-62.

1158-1164.

197.

449.

1996. 10: p. P3-3.

*response to acute psychosocial stress.* Psychoneuroendocrinology, 2006. 31(2): p. 151-

*hypothalamo-pituitary-adrenocortical responsiveness.* Front Neuroendocrinol., 2003.

*changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA* 

*degree, and background, but gender-neutral treatment.* Gender Medicine, 2007. 4: p.


Sex Differences and the Role of Sex Steroids in Sympatho-Adrenal

2001. 280(6): p. R1790-R1798.

R385.

R230.

375-380.

265-71.

86.

Medullary System and Hypothalamo-Pituitary Adrenal Axis Responses to Stress 135

[102] Keller-Wood, M. and C.E. Wood, *Pregnancy alters cortisol feedback inhibition of stimulated* 

[103] Pecins-Thompson, M. and M. Keller-Wood, *Effects of progesterone on blood pressure,* 

[104] Wood, C.E., et al., *Estrogen and androgen influence hypothalamic AVP and CRF concentrations in fetal and adult sheep.* Regul.Pept., 2001. 98(1-2): p. 63-68. [105] Keller-Wood, M. and C.E. Wood, *Effect of ovariectomy on vasopressin, ACTH, and renin* 

[106] Pecins-Thompson, M. and M. Keller-Wood, *Prolonged absence of ovarian hormones in the* 

[107] Genazzani, A.R., et al., *Evidence for a role for the neurosteroid allopregnanolone in the* 

[108] Patchev, V.K., et al., *The neurosteroid tetrahydroprogesterone counteracts corticotropin-*

[109] Patchev, V.K., et al., *The neurosteroid tetrahydroprogesterone attenuates the endocrine* 

[111] Wirth, M.M., et al., *Relationship between salivary cortisol and progesterone levels in humans.*

[112] Hermans, E.J., et al., *Exogenous testosterone attenuates the integrated central stress response in healthy young women.* Psychoneuroendocrinology, 2007. 32(8-10): p. 1052-61. [113] Hermans, E.J., N.F. Ramsey, and J. van Honk, *Exogenous testosterone enhances* 

[114] Wirth, M.M. and O.C. Schultheiss, *Basal testosterone moderates responses to anger faces in* 

[115] Lightman, S.L., et al., *Peripartum plasticity within the hypothalamo-pituitary-adrenal axis.*

[116] Tu, M.T., S.J. Lupien, and C.D. Walker, *Measuring stress responses in postpartum mothers: perspectives from studies in human and animal populations.* Stress., 2005. 8(1): p. 19-34. [117] Walker, C.D., D.J. Toufexis, and A. Burlet, *Hypothalamic and limbic expression of CRF and* 

[118] Neumann, I.D., *Alterations in behavioral and neuroendocrine stress coping strategies in pregnant, parturient and lactating rats.* Prog.Brain Res., 2001. 133: p. 143-152. [119] Uvnas-Moberg, K., *Oxytocin linked antistress effects--the relaxation and growth response.*

Biological Psychology, 2007. 74(1): p. 104-107.

*humans.* Physiol Behav, 2007. 90(2-3): p. 496-505.

*hyporesponsiveness.* Prog.Brain Res., 2001. 133: p. 99-110.

Acta Physiol Scand.Suppl, 1997. 640: p. 38-42.

Psychiatry, 2008. 63(3): p. 263-70.

Prog.Brain Res., 2001. 133: p. 111-129.

*the rat hypothalamus.* Neuropsychopharmacology, 1996. 15(6): p. 533-40. [110] Childs, E., N.T. Van Dam, and H. de Wit, *Effects of acute progesterone administration upon* 

*corticotropin-releasing factors.* Endocrinology, 1994. 134: p. 678-684.

*ACTH: studies in adrenalectomized ewes.* Am.J.Physiol Regul.Integr.Comp Physiol,

*plasma volume, and responses to hypotension.* Am.J.Physiol, 1997. 272(1 Pt 2): p. R377-

*activity responses to hypotension.* American Journal of Physiology, 1991. 261: p. R223-

*ewe reduces the adrenocorticotropin response to hypotension, but not to hypoglycemia or* 

*modulation of reproductive function in female rats.* Eur.J.Endocrinol., 1995. 133(3): p.

*releasing hormone-induced anxiety and alters the release and gene expression of corticotropin-releasing hormone in the rat hypothalamus.* Neuroscience, 1994. 62(1): p.

*response to stress and exerts glucocorticoid-like effects on vasopressin gene transcription in* 

*responses to acute psychosocial stress in men.* Exp Clin Psychopharmacol. 18(1): p. 78-

*responsiveness to social threat in the neural circuitry of social aggression in humans.* Biol

*vasopressin during lactation: implications for the control of ACTH secretion and stress* 


[84] Carter, J.R. and J.E. Lawrence, *Effects of the menstrual cycle on sympathetic neural responses* 

[85] Del Rio, G., et al., *Effect of estradiol on the sympathoadrenal response to mental stress in* 

[86] Critchlow, V., et al., *Sex difference in resting pituitary-adrenal function in the rat.* American

[87] Kaye, J., et al., *Responses to the 35% CO challenge in postpartum women.*

[88] Handa, R.J., et al., *Gonadal steroid hormone receptors and sex differences in the hypothalamo-*

[89] Kant, G.J., et al., *Comparison of stress response in male and female rats: pituitary cyclic AMP* 

[90] Mitsushima, D., J. Masuda, and F. Kimura, *Sex differences in the stress-induced release of* 

[91] Bohler, H.C., Jr., et al., *Corticotropin releasing hormone mRNA is elevated on the afternoon of* 

[92] Patchev, V.K. and O.F. Almeida, *Gender specificity in the neural regulation of the response to* 

[93] Vamvakopoulos, N.C. and G.P. Chrousos, *Evidence of direct estrogenic regulation of human* 

[94] Handa, R.J., M.J. Weiser, and D.G. Zuloaga, *A role for the androgen metabolite, 5alpha-*

[95] Buckingham, J.C., K.D. Dohler, and C.A. Wilson, *Activity of the pituitary-adrenocortical* 

[96] Viau, V. and M.J. Meaney, *Variations in the hypothalamic-pituitary-adrenal response to stress during the estrous cycle in the rat.* Endocrinology, 1991. 129(5): p. 2503-2511. [97] Smith, C.J. and R.L. Norman, *Influence of the gonads on cortisol secretion in female rhesus* 

[98] Bingaman, E.W., et al., *Androgen inhibits the increase in hypothalamic corticotropin-releasing* 

[99] Canny, B.J., et al., *Inlfuence of sex and gonadal status on the hypothalamo-pituitary- adrenal* 

[100] Bell, M.E., C.E. Wood, and M. Keller-Wood, *Influence of reproductive state on pituitaryadrenal activity in the ewe.* Domestic Animal Endocrinology, 1991. 8: p. 245-254. [101] Keller-Wood, M., J. Silbiger, and C.E. Wood, *Progesterone attenuates the inhibition of* 

*hormonal stress reactivity.* J Neuroendocrinol, 2009. 21(4): p. 351-8.

*macaques.* Endocrinology, 1987. 121: p. 2192-2198.

Neuroendocrinology, 1994. 59: p. 228-234.

Endocrinology, 1996. 1: p. P1-368.

*and plasma prolactin, growth hormone and corticosterone.* Psychoneuroendocrinology,

*acetylcholine in the hippocampus and corticosterone from the adrenal cortex in rats.*

*proestrus in the parvocellular paraventricular nuclei of the female rat.* Brain

*stress: new leads from classical paradigms.* Molecular Neurobiology, 1998. 16(1): p. 63-

*corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.* J.Clin.Invest, 1993.

*androstane-3beta,17beta-diol, in modulating oestrogen receptor beta-mediated regulation of* 

*system and thyroid gland during the oestrous cycle of the rat.* Journal of Endocrinology,

*hormone (CRH) and CRH-immunoreactivity following gonadectomy.*

*(HPA) axis of the sheep.* Proceedings of the 10th International Congress of

*adrenocorticotropin responses by cortisol in nonpregnant ewes.* Endocrinology, 1988. 123:

*pituitary-adrenal axis.* Hormones and Behavior, 1994. 28: p. 464-476.

*to mental stress in humans.* J Physiol, 2007. 585(Pt 2): p. 635-41.

*normal men.* J Clin Endocrinol Metab, 1994. 79(3): p. 836-40.

Journal of Physiology, 1963. 205: p. 807-815.

Clin.Endocrinol.(Oxf), 2004. 61(5): p. 582-588.

Neuroendocrinology, 2003. 78(4): p. 234-240.

Res.Mol.Brain Res., 1990. 8(3): p. 259-262.

1983. 8(4): p. 421-428.

92(4): p. 1896-1902.

1978. 78: p. 359-366.

p. 647-651.

77.


**Part 2** 

**Sex Steroids, Memory and the Brain** 

