The Histamine H4 Receptor Is Detected in Neonatal Human Leydig Cells, and in Prepubertal Leydig Cells Tumors. Possible Involvement in Neonatal Leydig Cells Pool Preservation

Presentation Number: THR-119
Date of Presentation: March 5th, 2015

Paula Aliberti1, Carolina Mondillo2, Adriana Maria Belen Abiuso2, Omar Pedro Pignataro2, Marco A. Rivarola3, Alicia Belgorosky4 and Esperanza Beatriz Berensztein*5
1Garrahan Pediatric Hospital, Buenos Aires, Argentina, 2Institute of Biology and Experimental Medicine (IBYME-CONICET), Buenos Aires, Argentina, 3Hospital de Pediatria Garrahan, Argentina, 4Hospital de Pediatría Garrahan, Buenos Aires, Argentina, 5Endocrine Service, Garrahan Pediatric Hospital, Buenos Aires, Argentina

Abstract

Histamine (HA) is an endogenous biogenic amine synthesized from L-histidine exclusively through the catalytic activity of histidine decarboxylase (HDC). HDC is expressed by testicular mast cells and germ cells (1). HA is now known to elicit a vast spectrum of physiological and pathological actions, including the pathogenesis of several tumors, through binding to four G protein-coupled receptors, designated as HRH1-4 (2). Accordingly, numerous studies have documented the ability of HA to modulate steroidogenesis through H1R and H2R in rodents Leydig cells, and their proliferation under pathological conditions [3]. In human testes of fertile and infertile patients, the expression of H1R, and H2R by germinal, interstitial, and peritubular cells was reported (4). The H4 receptor (H4R), the newest member of the family, is considered a promising drug target for allergy, inflammation, autoimmune disorders, and cancer [5]. Very recently, we reported for the first time that H4R is functionally expressed in murine Leydig cells, and that its selective activation can significantly inhibit gonadotropin-stimulated stereoidogenesis via a reduction in cAMP levels [6). However, there is no information available on HR4 expression in immature human testes.

Aim of the study: 1) to evaluate the developmental immunoexpression of H4R in normal immature human testis from neonatal period to late prepuberty, and 2) to compare the H4R immunoexpression pattern in normal immature testis vs Leydig cell tumors.

Material and Methods: Human normal testes (n=10) were collected at the time of necropsy from subjects without endocrine or metabolic diseases. For the analysis of results, samples were divided according to age: neonatal (< 1 month old, n=3), infant (postnatal activation, 1 to 7 months old, n=4), and prepubertal (stage of development devoid of morphologically identified LC), (1 to 12 years old, n=3). Leydig cell tumors were collected from two patients at time of surgery: 3.92- and 6.0-years old. Santa Cruz (sc-33967) specific anti-H4R antibody was used for immunohistochemistry.

Results: We detected positive H4R expression in cells exhibiting the characteristic histological appearance of Leydig cells (LC) in all normal newborns and in only the youngest of the four infants (age: 2 months). Positive H4R in some interstitial cells was also found. No H4R was detected in prepubertal testes. In contrast, LC tumors showed high H4R staining not only in tumor LC but also in inflammatory- or fibroblastic-like cells.

Conclusions: Since H4R was only detected in all neonatal and only in 1 infant human LC it could be proposed that HR4 pathway activation might be involved in the preservation of LC pool. This mechanism might also be involved in the in LC tumor development.

 

Nothing to Disclose: PA, CM, AMBA, OPP, MAR, AB, EBB