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Regulation of adrenal steroidogenic function; role and modulation of apoptosis (programmed cell death) in adrenocortical remodelingThe major focus of this laboratory is to understand how stress enhances the setpoint of adrenocortical cell function. The overall project goals are to determine whether stressors induce in the adrenal gland a greater proportion of cells having abnormally enhanced steroidogenic properties. by 1) exploiting the functional plasticity of the resident populations of adrenocortical cells and/or 2) stimulating the proliferation of new populations of cells having altered functional properties while concomitantly accelerating the death (apoptosis) of the resident populations of cells. For example. dietary protein restriction in the domestic fowl causes adrenal hypertrophy. and enhances the adrenocortical cell setpoint of response (corticosterone and aldosterone production) to adrenocorticotropic hormone (ACTH). This enhancement of function is accompanied by an increase in cellular ACTH receptor concentration and affinity. and signal transduction indices. However. paradoxically. cellular adenylyl cyclase activity is decreased. By contrast. in another nutritional stressor model. dietary sodium restriction. there is no hypertrophy. Although there is a differentially enhanced aldosterone response of a subpopulation of adrenocortical cells to angiotensin II (ANG II). there are no salient changes in cellular ANG II receptor parameters. Using these two nutritional stressor models. research is conducted at both cellular and molecular levels and is aimed at unraveling the relative roles that adrenocortical cell plasticity (i.e.. change in adrenocortical cell steroidogenic status and tropic hormone receptor parameters) and adrenocortical remodeling (i.e.. loss of resident cell populations by cell death and replacement with new cells having different functional characteristics) play in altering the adrenocoritcal setpoint. Selected PublicationsCarsia RV, McIlroy PJ, Cox RM, Barrett M, John-Alder HB. (2008) Gonadal modulation of in vitro steroidogenic properties of dispersed adrenocortical cells from Sceloporus lizards. Carsia RV. John-Alder HB. (2006) Natriuretic peptides are negative modulators of adrenocortical cell function of the eastern fence lizard (Sceloporus undulatus). Gen Comp Endocrinol. 145(2):157-61. Carsia RV. John-Alder H. (2003) Seasonal alterations in adrenocortical cell function associated with stress-responsiveness and sex in the eastern fence lizard (Sceloporus undulatus). Horm Behav.43(3):408-20. Liu P. Xu B. Forman LJ. Carsia R. Hock CE. (2002) bnL-NAME enhances microcirculatory congestion and cardiomyocyte apoptosis during myocardial ischemia-reperfusion in rats. Shock. 17(3):185-92. Carsia. R.V.. and Weber. H. (2000) Remodeling of turkey adrenal steroidogenic tissue induced by dietary protein restriction: The potential role of cell death. Gen. Comp. Endocrinol. 118: 471-479 Carsia. R.V.. and Weber. H. (2000) Dietary protein restriction stress in the domestic chicken (Gallus gallus domesticus) induces remodeling of adrenal steroidogenic tissue that supports hyperfunction. Gen. Comp. Endocrinol. 120:99-107. Carsia. R.V.. and Harvey. S. ( 2000) Adrenals. In: Sturkie's Avian Physiology. 5th edition. Whittow. G.C.. ed.. Chap. 19. pp. 489-587. Academic Press. McIlroy. P. J.. Kocsis. J. F.. Weber. H. and Carsia. R.V. (1999) Dietary protein restriction stress in the domestic fowl (Gallus gallus domesticus) alters adrencorticotropin (ACTH)-transmembranous signaling and corticosterone negative feedback in adrenal steroidogenic cells. Gen. Comp. Endocrinol. 113: 255-266. Carsia. R.V.. Nagele. R. G.. Morita. Y.. Tilly. K. I. and Tilly. J. L. (1998) Models to elucidate the regulation of adrenal cell death. In: Proceedings of the VIII Adrenal Cortex Conference. Endocr. Res. 24: 899-908. Carsia. R. V.. and McIlroy. P. J. (1998) Dietary protein restriction stress in the domestic turkey (Meleagris gallopavo) induces hypofunction and remodeling of adrenal steroidogenic tissue. Gen. Comp. Endocrinol. 109:140-153. |