Microtubule Acetylation in Anterior Pituitary Gonadotropes

Mikesell, JayCee
The hypothalamic pituitary gonadal (HPG) axis plays an essential role in mammalian reproduction. In the hypothalamus gonadotropin releasing hormone (GnRH) is released where it then travels to the anterior pituitary to bind to its receptor on gonadotrope cells inducing synthesis and release of luteinizing hormone (LH) and follicle stimulating hormone (FSH). Once in systemic circulation, LH and FSH act on the gonads to stimulate gametogenesis and steroid hormone synthesis. Vesicles filled with these hormones are formed in the endoplasmic reticulum, packaged in the Golgi apparatus, after which microtubule networks within the gonadotropes act as a highway to bring the vesicles toward the membrane for release. Microtubules consist of alpha and beta tubulin polymers, which can be modified post-translationally, aiding in the release of LH and FSH from anterior pituitary cells. It was hypothesized that GnRH binding its receptor leads to microtubule acetylation, a type of post-translational modification in which an acetyl group is added to tubulin polymers. To test this LβT2 cells underwent separate treatments of GnRH, insulin, and tubacin. These cells were lysed and used in western blots showing that GnRH leads to microtubule acetylation in a time dependent manner, that microtubule acetylation is specific to GnRH, and that a deacetylase inhibitor leads to microtubule acetylation in the absence of GnRH, respectively. Microtubules are an important part of the cytoskeleton, involved in the trafficking of secretory vesicles to the plasma membrane, and their acetylation due to GnRH binding in the anterior pituitary may aid in the transport and release of LH and FSH from gonadotropes.
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