Puberte nöroendokrinolojisi ve gonadotropin salgılatıcı hormon nöronları

Gonadotropin salgılatıcı hormon (GnRH), puberte oluşumunda temel olarak rol oynayan ve hipotalamusta çeşitli nöron gruplarından salınan bir hormondur. GnRH nöronları, belirli aralıklarla salınım yapmakta ve bu nedenle “Puls Jeneratörü” olarak adlandırılmaktadır. Kisspeptin ve reseptörü olan KiSS1R, GnRH salınımınında anahtar faktörlerdir. Kisspeptin ile uyarılan GnRH salınımı ile birlikte ön hipofiz üreme hormonları olan luteinleştirici hormon (LH) ve folikül uyarıcı hormon (FSH) salınır. Ön hipofizden salınan bu hormonlar, gonadların gelişmesini, işlevlerini yerine getirmesini ve olgunlaşmasını sağlar. Puberte oluşumundan önce juvenil duraklama süreci içerisinde GnRH puls jeneratörü baskılanmıştır ve gonadotropin salınımı engellenmiştir. Engelin kalkması ile birlikte puberte meydana gelmektedir. Puberte oluşumu ile beraber GnRH salınımının sıklığı ve genliği artar ve bunun sonucu LH ve FSH salınımları da artar. Sonuç olarak ikincil cinsel özellikler meydana gelir. Puberte oluşumunda bir diğer önemli etken olarak ortaya çıkan hormon leptindir. Leptin düzeyi, vücut enerji deposu ile orantılı olup temel işlevi beyini vücut enerji rezervinden haberdar etmek ve obezite gelişimini engellemektir. Puberte oluşumunda leptin, bir enerji sinyali olarak görev yapar ve yeterli düzeyde enerji miktarına ulaşıldığında puberte öncesi artmakta ve yokluğunda puberte gecikmektedir. Bu derlemede, puberte ve GnRH nöronları arasındaki ilişki, puberte oluşumunun öncesi ve sonrasında meydana gelen hormonal değişimler ve olası puberte oluşum mekanizması tartışılacaktır

Ultrastructural Interrelationship between the Pineal Gland and the Testis in the Male Rat

The ultrastructural interrelationship between the pineal gland and testis was evaluated in the rat. Wistar rats were divided into 6 groups. Groups I and II were sham-orchidectomized and orchidectomized rats, respectively. Rats in group III were orchidectomized and daily injected with testosterone propionate (TP) for 1 month. Groups IV and V were sham-pinealectomized and pinealectomized, respectively. Group VI was pinealectomized and daily injected with melatonin for 2 months. All animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II, and III and the testes of groups IV, V, and VI were removed and weighed. All specimens were examined by electron microscopy. Orchidectomy caused an increase of lipid droplets, cytoplasmic dense bodies, and lysosomes. Rough endoplasmic reticulum, Golgi apparatus, and mitochondria were extensive in the cytoplasm. TP administration to orchidectomized rats resulted in formation of less extensive lipid droplets and mitochondria. In pinealectomized rats, golgi complex, mitochondria, and enlarged smooth endoplasmic reticulum were extensive in the cytoplasm of Leydig cells. Formation of cytoplasmic secretory granules and osmiophilic bodies was observed. Testicular weight increased compared to group IV. Melatonin decreased testicular weight in comparison to group V and prevented ultrastructural changes. Pinealectomy and orchidectomy caused hyperactivity in Leydig cells and pinealocytes, respectively, which suggests a mutual relationship between the pineal gland and testis in the rat

Effects of long‐term paroxetine or bupropion treatment on puberty onset, reproductive and feeding parameters in adolescent male rats

Antidepressant use in adolescents has become more common in recent years. We have found several studies stating that prenatal antidepressant exposure can lead to delayed or earlier puberty onset but there was no study on postnatal paroxetine or bupropion. The main aim of this study was to investigate the effect of postnatal exposure to bupropion or paroxetine on puberty onset, reproductive and feeding results. The male rats (n = 8/group) aged 21 days were exposed to paroxetine (3.6 mg/ kg) or bupropion (17 mg/kg) orally by gastric gavage every day from postnatal day 21–90. Also, control group received only saline orally as a vehicle. Postnatal exposure to bupropion or paroxetine delayed puberty onset compared to control group, but it was not significant. Sperm counts were significantly lower in the paroxetine and bupropion groups compared to control group. Sperm motility was significantly lower in only bupropion group. In addition, sperm motility was lower in paroxetine group, but it was not significant. In the histopathological examination, there was damage to the testicular structure in both treatments. Taken together, our result indicates that postnatal paroxetine or bupropion exposure may affect puberty onset and contribute to the impairment in fertility in male rats.TÜBİTAK (113S193

Studies on the reproductive effects of chronic treatment with agomelatine in the rat

Agomelatine is an antidepressant with a novel mechanism of action. It is a melatonergic agonist for MT1 and MT2 receptors and a serotonin (5-HT2C) receptor antagonist. Agomelatine has been suggested not to have adverse effects on sexual functions. However, the effects of chronic agomelatine administration on reproductive functions have not been sufficiently studied in animal models. We mainly aimed to explore the effects of agomelatine on reproductive functions in the male and female rats. For the experimental studies, Sprague Dawley rats were used. The animals started to receive daily oral agomelatine (10mg/kg) on post-natal day 21. Agomelatine advanced vaginal opening in the female rats whereas it delayed puberty onset in the male rats. Agomelatine treatment significantly decreased intromission frequencies, which indicates a facilitator role of this antidepressant on male sexual behavior. In the forced swimming test (FST) used for assessing antidepressant efficacy, agomelatine induced a significant decrease in duration of immobility, and an increase in the swimming time, respectively, which confirms the antidepressant-like activity of agomelatine. The present findings suggest that agomelatine shows a strong antidepressant effect in the male rats without any adverse influences on sexual behavior, and its effects on pubertal maturation seem to show sex-dependent differences.TÜBiTAK – 113S19

Puberte nöroendokrinolojisi ve gonadotropin salgılatıcı hormon nöronları

Gonadotropin salgılatıcı hormon (GnRH), puberte oluşumunda temel olarak rol oynayan ve hipotalamusta çeşitli nöron gruplarından salınan bir hormondur. GnRH nöronları, belirli aralıklarla salınım yapmakta ve bu nedenle “Puls Jeneratörü” olarak adlandırılmaktadır. Kisspeptin ve reseptörü olan KiSS1R, GnRH salınımınında anahtar faktörlerdir. Kisspeptin ile uyarılan GnRH salınımı ile birlikte ön hipofiz üreme hormonları olan luteinleştirici hormon (LH) ve folikül uyarıcı hormon (FSH) salınır. Ön hipofizden salınan bu hormonlar, gonadların gelişmesini, işlevlerini yerine getirmesini ve olgunlaşmasını sağlar. Puberte oluşumundan önce juvenil duraklama süreci içerisinde GnRH puls jeneratörü baskılanmıştır ve gonadotropin salınımı engellenmiştir. Engelin kalkması ile birlikte puberte meydana gelmektedir. Puberte oluşumu ile beraber GnRH salınımının sıklığı ve genliği artar ve bunun sonucu LH ve FSH salınımları da artar. Sonuç olarak ikincil cinsel özellikler meydana gelir. Puberte oluşumunda bir diğer önemli etken olarak ortaya çıkan hormon leptindir. Leptin düzeyi, vücut enerji deposu ile orantılı olup temel işlevi beyini vücut enerji rezervinden haberdar etmek ve obezite gelişimini engellemektir. Puberte oluşumunda leptin, bir enerji sinyali olarak görev yapar ve yeterli düzeyde enerji miktarına ulaşıldığında puberte öncesi artmakta ve yokluğunda puberte gecikmektedir. Bu derlemede, puberte ve GnRH nöronları arasındaki ilişki, puberte oluşumunun öncesi ve sonrasında meydana gelen hormonal değişimler ve olası puberte oluşum mekanizması tartışılacaktır

Leptin regulation of pubertal maturation in intact and pinealectomized female rats

Aim: To explore the roles of leptin and melatonin in early pubertal maturation. Materials and methods: Wistar female rats were used as experimental animals. Leptin was subcutaneously infused for 28 days through osmotic minipumps starting from postnatal day 15 (preweaning). Pinealectomy was performed on postnatal day 21 (weaning), and the animals were decapitated when estrus was detected by vaginal smearing. Results: Chronic preweaning, by peripheral infusion of leptin through subcutaneous routes, advanced the onset of puberty in leptintreated sham and pinealectomized groups as determined by vaginal opening, while causing no significant change in serum estradiol levels and uterus weight. Mean body weights on the day of vaginal opening were significantly lower (P < 0.01) in leptin and pinealectomizedleptin groups compared to the control group. Conclusion: Preweaning leptin administration advances the onset of puberty regardless of body weight, and the pineal gland does not seem to have a modulatory effect on leptin-induced pubertal maturation. © TÜBİTAK

Effect of Melatonin on Role of Food İntake Regulator Neurotransmitters in Rats

Amaç: Melatoninin gıda alımı üzerine etkisi ile ilgili, farklı türlerde çelişkili sonuçlar içeren önemli çalışmalar mevcuttur. Bu çalışmadaki amacımız melatoninin gıda alımının düzenlenmesinde rolü olan Lateral Hipotalamik Nükleus (LHA), Ventromedial Hipotalamik Nükleus (VMN) ve Nükleus Akkumbens (NAC) bölgelerindeki nörotransmitterler ile metabolitleri üzerine etkisinin olup olmadığını araştırmaktı. Gereç ve Yöntem: Çalışmada 16 adet wistar albino cinsi sıçan kullanıldı. Yirmidört saat aç bırakılan sıçanlar iki gruba ayrıldı ve bir gruba intraperitoneal melatonin (2mg/kg) verildi. Kontrol grubuna ise çözücü enjekte edildi. Enjeksiyonlardan yarım saat sonra hayvanlar dekapite edilerek beyin dokuları alındı. Mikro panç tekniği ile VMN, LHA ve NAC çıkarılarak homojenize edildi ve Elektrokimyasal Detektörlü, Yüksek Performanslı Sıvı Kromotografisi (HPLC-ECD) yöntemiyle dopamin, noradrenalin ve bunların metabolitlerinin tayini yapıldı. Bulgular: Melatonin, LHA’da noradrenalin ve dihidroksi fenilglikol (DHPG) değerlerinde artışa neden olurken, VMN’da sadece noradrenalin artırmıştır. NAC’de ise noradrenalin değerini anlamlı bir şekilde azaltırken DHPG değerini artırmıştır. Bu nükleusta dopamin ve 3,4-dihidroksi fenilasetikasit (DOPAC) değerlerinde ise herhangi bir değişiklik oluşturmamıştır. Sonuç: Melatoninin LHA’daki noradrenalin ve DHPG değerlerinde artışa neden olması gıda alımını azaltıcı bir etkiye sahip olabileceğini göstermektedir. Aynı şekilde NAC’deki noradrenalin değerindeki azalma da yine melatoninin gıda alımını azaltıcı bir etkiye sahip olabileceğini göstermiştir.Objective: Effects of melatonin on food intake in various species have been important studies with contradictory implications. In this study, we have aimed to investigate the modulatory effects of melatonin on noradrenergic and dopaminergic neurotransmitters in brain areas, LHA, VMN and NAC, which are involved in the regulation of food intake. Materials and Methods: In this study, 16 wistar albino rats were used. Adult male Wistar rats were divided into two groups and fasted for 24 hours. The first groups of animals were intraperitoneally injected with melatonin (2 mg/kg). Controls received ethanol saline alone. All animals were decapitated 30 mins after injections and brains rapidly removed. LHA, NAC and VMN were isolated from frozen brain clices by micropunch technique. Catecholamine content of these brain samples was determined by High Performance Liquid Chromotography- Electrochemical Detector (HPLC-ECD). Results: Administration of melatonin significantly elevated concentrations of noradrenaline and its metabolite, DHPG in LHA and VMN (except DHPG). In the NAC, noradrenaline values were reduced, but DHPG was increased. No significant changes were seen in dopamin and DOPAC levels in NAC. Conclusion: Melatonin caused an increase noradrenaline and DHPG value in the LHA. This effect of melatonin might be decreased food intake. At the same time melatonin has effects of decrease of noradrenaline value in NAC. These effects show that melatonin could be decreased food intake

Effects of Peripheral Administration of Kisspeptin on Pubertal Maturation and Serum Leptin Levels in Female Rats

Objective: The aim of this study was to investigate the effects of exogenous kisspeptin on pubertal maturation in immature female rats. Material and Methods: Wistar female rats were weaned when they were 21 days old. The rats were divided into two groups. Controls (n=10) received saline only (1 ml/kg). Experimental rats (n=9) were intraperitoneally injected with daily 100 nmol kisspeptin-10 between 09.00h-10.00h a.m. starting from the day 26. Body weight and food intake were daily determined, and vaginal opening (VO) was daily monitored starting from day 26. The animals were decapitated when the first diestrus was determined by vaginal smears. Upon decapitation, serum was separated and stored at -20°C until measurement of leptin, luteinizing hormone (LH) and estradiol. Uterus and ovaries were dissected out and weighed. Results: Intrape-ritoneal injection of 100 nmol kisspeptin-10 did not change median VO ages. There were no differences in food intake, and percentages of body weight change, between control and kisspeptin groups during the experimental period. Kisspeptin administration elicited significant (P<0.01) increases in uterus weight over control values. Serum leptin levels were significantly lower (P<0.05) in kisspeptin-treated group compared to vehicle group. Kisspeptin administration increased (P<0.05) serum LH and estradiol levels. Conclusion: Chronic peripheral administration of kisspeptin-10 does not advance puberty onset as estimated from the date of vaginal opening, but potentiates other conventional indices of maturation of reproductive axis such as elevated uterine weight and increased serum levels of LH and estradiol. © 2011 by Türkiye Klinikleri