Identification of a catecholamine- and drug-target, the α2A-adrenoceptor, in human testis and human testicular perit-ubular cells

ABSTRACT: Abstract: Clonidine has been used in clinical medicine, e.g. to treat high blood pressure, and its use has been linked to impairments of male fertility, but the underlying reasons are not known. Clonidine is an agonist at the α2A-adrenoceptor (ADRA2A) which is expressed by cells of the testis, hence interference at the testicular level is plausible to assume. Because the human testis and its cells are not readily accessible to experimental testing, we used cultured human testicular peritubular cells (HTPCs), which represent a unique experimental window into the human peritubular wall compartment to clarify direct actions of this antihypertensive drug. Immuno-histochemical / immuncytochemical and PCR techniques proved ADRA2A expression in human testis and cultured HTPCs. Clonidine when tested over a concentration range (1-1000 µM) did not visibly affect HTPC morphology and no obvious toxic actions became apparent over a 24 h period. Already at 1 µM, clonidine significantly stimulated IL6 mRNA, yet most effective increase was found at 10 µM which was used for further studies. ELISA measurements confirmed this action of clonidine. In gel contraction assays, clonidine exerted a slight relaxing action. Results of a pro-teomic study revealed that the exposure to clonidine for 24 h did not significantly change protein abundance of HTPCs. Thus, ADRA2A, is expressed in the human testis, among others in perit-ubular cells and represents a target of clonidine, other drugs and natural catecholamines. Based on our studies in HTPCs, such agonists of ADRA2A may have the potential to interfere with human testicular functions.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Peritubular Myoid Cell, Cell Culture

DISEASE(S): Azoospermia

SUBMITTER: Youli Konstantinovitch Stepanov  

LAB HEAD: Dr. Thomas Fröhlich

PROVIDER: PXD052220 | Pride | 2024-10-17

REPOSITORIES: Pride