Abstract

Patients with epilepsy experience a variety of endocrine-related problems, of which the most widely reported is the effect on sexual function. A precise etiology for the effect on sexual function has not been established. Both a direct effect on steroid hormone levels and an indirect CNS effect have been suggested.
The specific aims of this proposal are based on the hypothesis that antiepileptic drugs (AEDs) cause endocrine-related effects by interacting with adrenal and gonadal enzymes involved in steroid synthesis and/or hepatic enzymes involved in steroid degradation. Specifically, we evaluated the effects of the AED known as valproic acid. Adrenal glands, liver, testicles and ovaries from Macaca nemestrina were obtained from the tissue program at the Washington RPRC. In the initial studies we determined the optimal culture conditions for adrenal glands, testes and ovaries. Valproic acid had a direct effect on cortisol production in adrenal cells and estradiol production in ovarian and testicular cells, suggesting that the endocrine side effects of valproic acid are caused by direct interaction with the enzymes involved in steroid synthesis and/or degradation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000166-38
Application #
6116391
Study Section
Project Start
1999-05-01
Project End
2000-04-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
38
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of Washington
Department
Type
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Hasegawa, Yu; Curtis, Britni; Yutuc, Vernon et al. (2018) Microbial structure and function in infant and juvenile rhesus macaques are primarily affected by age, not vaccination status. Sci Rep 8:15867
Oleskiw, Timothy D; Nowack, Amy; Pasupathy, Anitha (2018) Joint coding of shape and blur in area V4. Nat Commun 9:466
Pham, Amelie; Carrasco, Marisa; Kiorpes, Lynne (2018) Endogenous attention improves perception in amblyopic macaques. J Vis 18:11
Zanos, Stavros; Rembado, Irene; Chen, Daofen et al. (2018) Phase-Locked Stimulation during Cortical Beta Oscillations Produces Bidirectional Synaptic Plasticity in Awake Monkeys. Curr Biol 28:2515-2526.e4
Choi, Hannah; Pasupathy, Anitha; Shea-Brown, Eric (2018) Predictive Coding in Area V4: Dynamic Shape Discrimination under Partial Occlusion. Neural Comput 30:1209-1257
Shushruth, S; Mazurek, Mark; Shadlen, Michael N (2018) Comparison of Decision-Related Signals in Sensory and Motor Preparatory Responses of Neurons in Area LIP. J Neurosci 38:6350-6365
Raghanti, Mary Ann; Edler, Melissa K; Stephenson, Alexa R et al. (2018) A neurochemical hypothesis for the origin of hominids. Proc Natl Acad Sci U S A 115:E1108-E1116
Wool, Lauren E; Crook, Joanna D; Troy, John B et al. (2018) Nonselective Wiring Accounts for Red-Green Opponency in Midget Ganglion Cells of the Primate Retina. J Neurosci 38:1520-1540
Eberle, R; Jones-Engel, L (2017) Understanding Primate Herpesviruses. J Emerg Dis Virol 3:
McAdams, Ryan M; McPherson, Ronald J; Kapur, Raj P et al. (2017) Focal Brain Injury Associated with a Model of Severe Hypoxic-Ischemic Encephalopathy in Nonhuman Primates. Dev Neurosci 39:107-123

Showing the most recent 10 out of 320 publications