Luteiniseeriva hormooni (LH) retseptori esinemine peenises ja selle võimalik roll erektsioonihäirete patogeneesis

Väitekirja elektrooniline versioon ei sisalda publikatsiooneSeoses 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 tekkesIn 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

EXPRESSION OF cAMP AND CREB IN THE HUMAN PENIS

The aim of this study is to investigate the expression of adenosine 3',5'-cyclic monophosphate (cAMP) and cAMP-response element-binding protein (CREB) in the human penis as it is known that luteinizing hormone (LH) regulates cellular function mostly through the cAMP signaling pathway and LH receptors are expressed by the penile endothelium. Penile tissue was obtained from three patients during partial or total penectomy due to a rectal cancer with secondary penile metastasis or squamous cell carcinoma of the penis. Immunohistochemistry was used for the detection of cAMP and CREB. Positive immunoreaction for cAMP was present in most cells of superficial, intermedial, and basal layer of urethral epithelium and in fibroblast-like cells (FLC) of interstitial tissue and endothelial cells (EC) of cavernous spaces in corpus spongiosum penis. Positive staining for cAMP was also visible in EC of cavernous spaces and in FLC of interstitial tissue in corpus cavernosum penis. Positive immunoreaction for CREB was present in the superficial and intermedial layer of urethral epithelium, and some positive immunoreaction was also noticed in EC of cavernous spaces and in FLC of interstitial tissue in corpus spongiosum penis. Positive staining was also visible in the EC of cavernous spaces and in fibroplast-like cells of the interstitial tissue in the corpus cavernosum penis. Our results show the presence of cAMP and CREB in the human penis. While LH exerts its actions through cAMP signaling system and our previous studies have shown the expression of luteinizing hormone/choriogonadotropin (LHCG) receptor in the mouse and human penis, this finding may support the hypothesis that LH could affect the spongious and cavernous tissue of the human penis and thereby influence the development of erectile dysfunction among aging men.Peer reviewe