sarah_dickerson@mail.utexas.edu
Former Ph.D. Student in Pharmacology/Toxicology
Background:
I graduated from Sam Houston State University in 2001 with a B.S. in Biology. Following graduation, I worked as an analytical chemist until I began my graduate career at the University of Texas at Austin in June 2004. My research has been generously funded by a one-year appointment to the Toxicology Training Grant, followed by a three-year National Science Foundation Graduate Research Fellowship. A UT University Continuing Fellowship currently supports my research efforts.
Research:
My research focuses on the impact of a class of environmental toxicants known as endocrine disrupting chemicals (EDCs) on the development of brain regions that control reproduction. There are distinct morphological and functional differences between male and female central nervous systems, a phenomenon known as sexual dimorphism. These differences are predominantly regulated by steroid hormones, and are permanent, taking shape during perinatal development. The early organizational effects of hormones on the developing nervous system are critical. If they are disrupted, adult reproductive sexual behaviors and reproductive physiology are permanently compromised. The goal of my dissertation research is to elucidate the cellular and molecular mechanisms by which normal developmental brain sexual differentiation is disrupted by polychlorinated biphenyls (PCBs), a class of persistent EDCs. In my experimental model, developing fetal rats are exposed to PCBs during brain sexual differentiation. My hypothesis is that PCBs perturb normal developmental apoptosis (programmed cell death) in brain regions that contribute to sexual differentiation of the brain in infancy, leading to latent abnormalities in the attainment of adult reproductive function. To this end, I am investigating a group of cells in the neuroendocrine hypothalamus that control reproductive function. This population of neurons synthesizes and releases a peptide called gonadotropin-releasing hormone (GnRH). In order for GnRH neurons to function properly, they require regulatory inputs from other hypothalamic brain regions, and my study focuses on one of the most sexually dimorphic regions in this regard: the anteroventral periventricular nucleus (AVPV). In this region, neurons that express estrogen receptor alpha (ERa) and kisspeptin (KISS) send projections to the GnRH neurosecretory system, and play an important role in pubertal onset, as well as ovulation and maintenance of estrus cycles in females via activation of GnRH neurons. Moreover, the expression pattern is sexually dimorphic, with females having a greater number than males. I’ve found that one of the repercussions of prenatal PCB treatment is a sex-dependent effect on pubertal onset, with an advancement of puberty observed in females and a delay in males. A potential mechanism through which EDCs disrupt maturation of neuroendocrine reproductive systems is through alteration of the sexually dimorphic expression pattern of ERa/KISS expressing neurons in the AVPV, thus interfering with normal transmission of regulatory/activational inputs onto the GnRH neurosecretory system. Interestingly, protein expression of ERa and KISS at early adulthood is reduced by PCBs in the female AVPV, but not affected in males. In addition, I am currently investigating whether perinatal EDC exposure interferes with GnRH activation during the afternoon of proestrus. These studies suggest that early life exposure to environmental EDCs may reprogram development of sexually dimorphic neuronal circuits involved in neuroendocrine control.
Publications:
Dickerson SM, Cunningham SL, and Gore AC (2010). Neuroendocrine HPG targets of developmental exposure to endocrine disruptors. In: Endocrine Disruptors and Puberty. ed. E Diamanti-Kandarakis and AC Gore. (In preparation)
Dickerson SM, Guevara E, Woller MJ, and Gore AC. (2009). Cell death mechanisms in GT1-7 GnRH cells exposed to polychlorinated biphenyls PCB74, PCB118, and PCB153. Toxicology and Applied Pharmacology. 237(2):237-245.
Dickerson SM, Walker DM, Reveron ME, Duvauchelle CL and Gore AC (2008). The Recreational Drug Ecstasy Disrupts the Hypothalamic-Pituitary-Gonadal Reproductive Axis in Adult Male Rats. Neuroendocrinology. 88(2):95-102.
Dickerson SM and Gore AC (2007). Estrogenic environmental endocrine-disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle. Reviews in Endocrine and Metabolic Disorders. 8(2):143-159.
Sailer BL, Liles N, Dickerson S, Sumners S and Chasteen TG (2004). Organotellurium Compound Toxicity in a Promyelocytic Cell Line Compared to a Non-Tellurium Containing Organic Analog. Toxicology in Vitro. 18:475-482.
Sailer BL, Liles N, Dickerson S and Chasteen TG (2003). Cytometric Determination of Novel Organotellurium Compound Toxicity in a Promyelocytic (HL-60) Cell Line Archives of Toxicology. 77:30-36.
Sailer BL, Prow T, Dickerson S, Watson J, Liles N, Patel SJ, Van Fleet-Stalder V and Chasteen TG (1999). Bacterial Cytotoxicity and Induction of Apoptosis in Promyelocytic (Line HL-60) Cells by Novel Organotellurium Compounds. Environmental Toxicology and Chemistry. 18(12):2926-2933.
