PARENT SESSION
TRAINEE RESEARCH COMPETITION
Haborside Foyer
7:30 AM-10:00 AM

(68) EVIDENCE THAT GABA-MEDIATED SEXUAL DIFFERENTIATION OF ARCUATE ASTROCYTES IS NECESSARY, BUT NOT SUFFICIENT, TO PREVENT HORMONAL INDUCTION OF AN LH-SURGE IN RATS.

Mong, Jessica¹, Alt, Jesse², Miele, Francesca², Legan, Sandra⁵, Gregerson, Karen⁶, Le, Wei Wei³, Hoffman, Gloria^3,4, McCarthy, Margaret^2,4, ¹ 1Laboratory of Neurobiology and Behavior, New York, NY² Departments of Physiology, Baltimore, MD⁵ Dept of Physiology, Lexington, KY⁶ Dept. of Physiology, St. Louis, MO³ Anatomy and Neurobiology, Baltimore, MD⁴ Program in Neuroscience, Baltimore, MD

ABSTRACT- The secretion of gonadotropic hormones from the anterior pituitary regulates estradiol secretion from the ovary and is centrally regulated by the activity of gonadotropic hormone releasing hormone (GnRH) neurons located in the hypothalamus. GnRH neuron terminals are located in the arcuate nucleus (ARC) and astrocytes residing in this region have been implicated in the regulation GnRH release and the subsequent LH surge in female rats. A marked sexual dimorphism in ARC astrocyte morphology is present by birth, with males having complex stellate cells compared to the simple bipolar ones found in females. This sex difference lasts throughout life, is a consequence of early estrogen action, and is mediated by the diffusible neuronal factor, GABA. Reducing GABA synthesis with antisense oligonucleotides (ODN) against glutamic acid decarboxylase (GAD) during the first few days of life prevents masculinization of ARC astrocytes, while administration of the GABAA agonist, muscimol induces masculinization in the absence of exogenous steroid. Here, we demonstrate that attenuation of astrocyte masculinization in males leads to an increase in LH levels. Males, females and neonatally androgenized females were treated with antisense oligonucleotides against GAD or muscimol and raised to adulthood, gonadectomized and hormonally treated to induce an LH surge. Females exhibited a robust surge in LH and the majority of LHRH neurons were active regardless of treatment as demonstrated by c-fos detection. Males had very low levels of LH with the exception of those treated neonatally with ODN GAD in which LH levels were approximately half those of females. There was no c-fos detected in LHRH neurons of males regardless of treatment but there was a significant increase in LHRH neurons characterized by a large swollen appearance, possibly indicative of activation. Androgenized females released little LH and there was little to no c-fos in LHRH neurons regardless of treatment.

KEY WORDS: Neuronal-glial interactrion, Arcuate, Estrogen, GnRH