Luteinizing hormone (LH) receptor expression in the penis and its possible role in pathogenesis of erectile disturbances

Abstract

Seoses elanikkonna vananemisega arenenud riikides on potentsiga seotud uuringud kaasaja teaduses aktuaalseks teemaks. Arvatakse, et aastaks 2025 esineb erektsioonihäireid ligikaudu 322 miljonil mehel kogu maailmas. Märkimisväärselt suurel osal vanemaealistest meestest on leitud erinevate suguhormoonide taseme muutusi. Võimalik, et vananevate meeste kõrgenenud luteiniseeriva hormooni (LH) kontsentratsioon mõjutab peenise kude ja on seeläbi seotud erektsioonihäirete tekkega. Sellise hüpoteesi eelduseks on LH retseptori ekspressioon peenises. Ajuripatsi eessagara gonadotropiin, LH, on üks tähtsamaid sugunäärmete talitluse reguleerijaid, avaldades objektrakkudele toimet läbi nende plasmamembraanil olevate retseptorite. LH reguleerib munandis spermatogeneesi ning steroidogeneesi, munasarjas folliikulite kasvu, ovulatsiooni, kollaskeha arengut ning steroidide tootmist. Lisaks mees- ja naissugurakkudele on LH- d leitud erinevate liikide mittegonadaalsetes kudedes, sealhulgas platsentas, emakas, ajus, eesnäärmes, munajuhas ja munandimanuses. Käesoleva doktoritöö uuringud viidi läbi koostöös Tampere Ülikooli anatoomia osakonnaga ja Tampere Ülikooli Kliinikumiga ning uurimuse

eesmärk on hinnata LH- retseptori ja selle signaaliülekandjate ( cAMP ja CREB) esinemist peenises. Uuringud viidi läbi hiire ja inimese peenise koel, kasutades Western blottingu, kvantitatiivse RT-PCR-i ja immunohistokeemia meetodit ning saadi positiivsed tulemused kõigi uurimismeetoditega. LH retseptori antigeen tuvastati nii hiire kui inimese peenises. Tugev positiivne immunoreaktsioon LH retseptorile saadi nii hiire kui ka inimese peenise erinevates rakkuliikides. Positiivne immunoreaktsioon cAMP-ile ja CREB- ile saadi inimese peenise koes. Pole veel selge, mis funktsioon LH retseptoril peenises on, kuid on võimalik, et suurenenud seerumi LH tase mõjutab peenise kude ja osaleb seeläbi erektsioonihäirete tekkes

In the context of an aging population in developed countries, research related to potency is an important issue in modern science. A large number of older men experience changes in the level of different sex hormones. It is predicted that by 2025 over 322 million men are affected by erectile dysfunction worldwide. It is possible that high luteinizing hormone (LH) levels in aging men may have an impact on the penile tissue and are thereby related to the development of erectile dysfunction. The prerequisite for such hypothesis would be the expression of LH receptors in the penis. LH belongs to the family of glycoprotein hormones and is produced in the anterior pituitary gland. In the male, LH regulates the spermatogenesis and steroidogenesis in the testes by acting through plasma membrane receptors. LH acts via binding to its receptor, and, besides male and female gonadal cells, number of laboratories worldwide have demonstrated the presence and functions of LH receptors in various female and male nongonadal tissues in different species. Its expression in the penis has never been studied before. The studies of this doctoral dissertation were conducted in cooperation with Department of Anatomy of Tampere University and Tampere University Hospital, and the general aim of the present study was to evaluate the expression of the LH receptor and the components of its signal transduction pathway, adenosine 3’,5’- cyclic monophosphate (cAMP) and cAMP-response element-binding protein (CREB) in the penis tissue. The studies were carried out on the mouse and human penis tissue by using Western blotting, quantitative reverse transcriptase polymerase chain (qRT-PCR) and immunohistochemistry methods. The LH receptor antigen was present in both mouse and human penises. A strong positive immunoreaction to LH was found in different cell types of mouse and human penises. A positive immunoreaction for cAMP and CREB was also present in human penis tissue. It is not clear yet what functions the LH receptor may have in the penis, but it is possible that elevated serum LH levels could affect the penis tissue and, thereby, have a role in the pathogenesis of erectile dysfunction.