Possible hypothalamic laterality in the central regulation of GnRH release: thoughts that might lead to a novel approach in hypothalamic studies

Zsarnovszky, Attila and Tóth, István and Johnson, Trudy Scalise and Somogyi, Virág and Kiss, Dávid Sándor and Győrffy, Andrea and Goszleth, Gréta and Bartha, Tibor and Frenyó, Vilmos László (2012) Possible hypothalamic laterality in the central regulation of GnRH release: thoughts that might lead to a novel approach in hypothalamic studies. In: IBRO 2012 Workshop, 2012. január 19-21., Szeged.

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Abstract

The midcycle E2 surge induces a synaptic reorganization in the mediobasal hypothalamus (MBH), thus increasing the ratio of stimulatory/inhibitory synapses. This synaptic reorganization disinhibits GnRH neurons and leads to an LH surge. Synaptic functions are energy dependent and require mitochondrial ATP production. Ectonucleoside triphosphate diphosphohydrolase 3 (NTPDase3) may play a crucial role in the regulation of mitochondrial ATP levels in stimulatory MBH neurons. The positive gonadophin feedback involves the generation and function of large numbers of hypothalamic stimulatory synapses, thus, it might be associated with increased mitochondrial ATP production and increased mitochondrial respiration (mr). Anatomically, there are paired brain areas in the two hemispheres and unpaired structures along the anatomical midline. Distinct sides of paired brain areas usually regulate distinct physiological processes, rather than sharing roles to regulate the exact same functions. However, there are certain brain regions with no known functional differences between the two sides. One such brain area is the MBH, which has always been investigated as an unpaired midline structure despite its clearly symmetric anatomical characteristics. Investigation of mr in MBH synaptosomal fractions in our laboratory has indicated that besides ipsylateral intrahypothalamic differences (i.e., differences between the lateral and medial regions of the MBH on the same side) a functional laterality may exist between homologous areas of symmetric hypothalamic structures. Therefore, we have investigated mr rates, with special regard to ADP-dependent state 3 mr, in the MBH with isolated left and right sides. Our initial results imply that the MBH regulation of the E2-induced gonadotrophin surge is unilateral, and that there is an urging need for a technical solution to identify in vivo the dominant hypothalamic side that enters into the positive gonadotrophin phase of the estrous cycle.

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