This proposal is a further examination of the mechanism by which immobilization stress inhibits the testicular response to gonadotropin in male rats. Experiments will focus on the transmission of the stress signal to the testis, mediation (pituitary, adrenal, immune system and gonadal) of the stress effect on the testis, effect of stress on the LH transducing system in Leydig cells and identification of site or sites of the inhibitory lesion in the steroidogenic pathway. A second series of experiments will further investigate the role of proopiomelanocortin peptides (pituitary, immune system, and gonadal origin), CRH, glucocorticoids and angiotensin II (Ag II) in attenuating testicular steroid production during stress. The effect of stress on the dynamics of LH/HCG binding, the adenyl cyclase system, Gi unit, changes in intracellular calcium (Leydig cell populations and single cell; spectrofluorometry and image analysis), and protein kinase C activation in Leydig cells will be examined in the third series of experiments. We will further examine the site(s) of the stressed-induced lesion in the steroidogenic pathway. The effect of stress and regulators of stress responses on enzymes involved in cholesterol synthesis and mobilization, and the synthesis and metabolism of T will be investigated. These experiments will define the mechanism of stress-induced testicular hyposensitivity to gonadotropin, and the role that pituitary, immune and gonadal regulatory factors play in this process.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD023295-04A1
Application #
3323392
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1987-08-01
Project End
1994-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Morehouse School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30310
Akinbami, M A; Philip, G H; Sridaran, R et al. (1999) Expression of mRNA and proteins for testicular steroidogenic enzymes and brain and pituitary mRNA for glutamate receptors in rats exposed to immobilization stress. J Steroid Biochem Mol Biol 70:143-9
Akibami, M A; Mann, D R (1996) Mechanism of stress-induced attenuation of the testicular response to gonadotropin: possible involvement of testicular opioids, a pertussis toxin-sensitive G-protein, and phosphodiesterase. J Androl 17:10-6
Srivastava, R K; Akinbami, M A; Mann, D R (1995) Acute immobilization stress alters LH and ACTH release in response to administration of N-methyl-D,L-aspartic acid in peripubertal and adult male rats. Life Sci 56:1535-43
Orr, T E; Taylor, M F; Bhattacharyya, A K et al. (1994) Acute immobilization stress disrupts testicular steroidogenesis in adult male rats by inhibiting the activities of 17 alpha-hydroxylase and 17,20-lyase without affecting the binding of LH/hCG receptors. J Androl 15:302-8
Srivastava, R K; Taylor, M F; Mann, D R (1993) Effect of immobilization stress on plasma luteinizing hormone, testosterone, and corticosterone concentrations and on 3 beta-hydroxysteroid dehydrogenase activity in the testes of adult rats. Proc Soc Exp Biol Med 204:231-5
Orr, T E; Mann, D R (1992) Role of glucocorticoids in the stress-induced suppression of testicular steroidogenesis in adult male rats. Horm Behav 26:350-63
Orr, T E; Mann, D R (1990) Effects of restraint stress on plasma LH and testosterone concentrations, Leydig cell LH/hCG receptors, and in vitro testicular steroidogenesis in adult rats. Horm Behav 24:324-41
Mann, D R; Gould, K G; Collins, D C (1990) A potential primate model for bone loss resulting from medical oophorectomy or menopause. J Clin Endocrinol Metab 71:105-10
Mann, D R; Orr, T E (1990) Effect of restraint stress on gonadal proopiomelanocortin peptides and the pituitary-testicular axis in rats. Life Sci 46:1601-9
Mann, D R; Gould, K G; Collins, D C et al. (1989) Blockade of neonatal activation of the pituitary-testicular axis: effect on peripubertal luteinizing hormone and testosterone secretion and on testicular development in male monkeys. J Clin Endocrinol Metab 68:600-7

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