Proliferation and differentiation of adult Leydig cells are mainly completed in puberty. In many studies, apart from normal postnatal development process, it is widely indicated that, through administrating EDS, Leydig cell population is eliminated and regenerated. It is believed that osteocalcin released from osteoblasts, which is responsible for modulating bone metabolism, induces testosterone production in Leydig cells, independent of the HPG axis. In addition, INSL3 produced by Leydig cells, such as testosterone, plays a critical role in bone metabolism and is known to reflect the development process and functional capacities of Leydig cells. This study is aimed at investigating OC-mediated testosterone regulation and INSL3 synthesis during differentiation of adult Leydig cells that are independent of LH. For this purpose, male rats were divided into 2 groups: prepubertal normal rats and adult EDS-injected rats. Each group was divided into 4 subgroups in which GnRH antagonist or OC was applied. After adult Leydig cells completed their development, testicular tissue samples obtained from the sacrificed rats were examined by light-electron microscopic, immunohistochemical, and biochemical methods. Slight upregulation in 3βHSD, INSL3, and GPRC6A expressions along with the increase in serum testosterone levels was observed in groups treated with osteocalcin against GnRH antagonist. In addition, biochemical and microscopic findings in osteocalcin treated groups were similar to those in control groups. While there was no significant difference in the number of Leydig cells reported, the presence of a significant upregulation in INSL3 and GPRC6A expressions and the increase in serum testosterone and ucOC levels were observed. After evaluation of findings altogether, it is put forward that, for the first time in this study, although osteocalcin treatment made no significant difference in the number of Leydig cells, it increased the level of testosterone through improving the function of existing adult Leydig cells during normal postnatal development process and post-EDS regeneration. This positive correlation between osteocalcin-testosterone and osteocalcin-INSL3 is concluded to be independent of LH at in vivo conditions.

Erkeklerde spermatogenezin normal şekilde gerçekleşebilmesi için testislerin karın boşluğu dışında, vücuttan 2-3°C düşük sıcaklıkta skrotum adı verilen kese içerisine inmeleri gerekmektedir. Testis iniş mekanizması türler arasında farklılık göstermekle birlikte, testislerin intrabdominal seviyeden skrotuma inmeleri hormonal ve mekanik etkilere bağlı olarak transabdominal ve inguinoskrotal evreler sonunda gerçekleşmektedir. Kranial süspansör ligament dejenerasyonu ve gubernakular şişme reaksiyonu ile karakterize olan transabdominal evre Leydig hücrelerinden salınan INSL3 (İnsülin benzeri faktör-3) kontrolündedir. Testislerin inguinal kanaldan geçerek skrotuma indiği son evre olan inguinoskrotal evre ise androjen bağımlıdır. Testislerin iniş süreci INSL3 ve androjenler dışında, Sertoli hücrelerinden salınan MIS (Mülleryan inhibe edici madde), genitofemoral sinir uçlarından salınan CGRP (Kalsitonin gen-bağımlı peptid), peritoneal bir divertikül olan vaginal prosses, meme hattı altındaki MFP (Meme yağ yastıkçığı) ile Hox genlerinin rol oynadığı kompleks bir süreçtir. Testis iniş mekanizmasında meydana gelen herhangi bir aksaklık durumunda, infertilite ve testiküler kanser nedenleri arasında sayılan anorşi, refraktil testis, kriptorşidizm ve ektopik testis görülebilmektedir.

Purpose: The aim of the study explores probable toxic effects of vancomycin on kidney and analysis of the probable protective effects of melatonin. Materials and Methods: In this study, rats were randomly divided into 4 groups: the control group; the melatonin (10 mg/kg/day) group; the vancomycin-treated (200 mg/kg) group; and the vancomycin (200 mg/kg) + melatonin (10 mg/kg/day) group. Rats in the treatment group were given two doses of vancomycin a day with an interval of seven consecutive days and melatonin (10 mg/kg/day) once daily for seven consecutive days. The experiment was continued for 15 days. In each group, seven rats were grouped together. 15 days after the experiment, the rats were sacrificed under anesthesia and among all groups. Kidney tissues were collected and processed for further TNF- expression analysis, as well as histological analyses such as hematoxylin and eosin (H&E), Masson's tricrom, and Periodic acid schiff (PAS) staining to assess pathological severity. In addition, a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to evaluate apoptosis. Results: While vancomycin upregulated TNF-α expression, melatonin reduced levels of TNF-α immunoreactivity intensity and clearly improved pathological severity in rat kidneys. Further, melatonin significantly inhibited vancomycin-induced TUNEL-positive cell numbers. Conclusion: Melatonin has protective activity against vancomycin-induced pro-inflammatory and proapoptotic effects in kidneys during organ preservation time and improves kidney function.