Kronik Olarak İntraserebroventriküler Enjekte Edilen Histamin ve Antagonistlerinin Hipotalamo-Hipofizer-Aks Üzerindeki Etkisi

Öz

Merkezi sinir sistemi içerisinde nörotransmitter ve nöromodülatör etkiye sahip histamin, davranış durumunun, biyolojik ritmin, vücut ağırlığının, enerji metabolizmasının, termoregülasyonun, sıvı dengesinin, stresin ve üremenin düzenlenmesinde anahtar role sahiptir. Histaminin merkezi akut enjeksiyonlarının hipotalamo-hipofizer-gonadal (HPG) aks içerisinde etkili olduğunu ve histaminin merkezi H1 ve H2 reseptör-lerinin bu etkiye aracılık ettiğini gösterdik. Fakat çalışmalarda, histaminin ve histamin reseptör antagonistlerinin uzun süreli merkezi tedavilerinin HPG aks içerisindeki etkilerine dair açıklayıcı bir bilgi bulunmamaktadır. Çalışmada, kronik olarak intraserebroventriküler (i.s.v.) enjekte edilen histamin ve antagonistlerinin hipotalamo-hipofizer-gonadal (HPG) aksta rol oynayan, gonadotropin salgılatıcı hormonun (GnRH), folikül stimüle edici hormonun (FSH), lüteinleştirici hormonun (LH) ve testosteron hormonunun plazma seviyelerine etkileri araştırılmıştır. Çalışma Sprague-Dawley ırkı sıçanlarda gerçekleştirilmiştir. Histamin (100 nmol), histaminerjik H1 reseptör antagonisti klorfeni-ramin (100 nmol), histaminerjik H2 reseptör antagonisti ranitidin (100 nmol) veya histaminerjik H3/H4 reseptör antagonisti tiyoperamid (100 nmol) i.s.v. olarak 7 gün boyunca enjekte edilmiştir. Histamin ve antagonistlerinin kronik enjeksiyonu GnRH’nın plazma seviyelerinde anlamlı bir fark oluşturmamıştır. Kronik histamin veya klorfeniramin tedavisi sonucu plazma FSH seviyelerinde artış (p<0,05) ve LH ve testosteron (p<0,05) seviyelerinde ise bir düşüş gözlenmiştir. Kronik ranitidin veya tiyoperamid tedavisi ise plazma FSH düzeylerinde bir etki oluşturmamış fakat LH ve testosteron seviyelerinde artışlara neden olmuştur (p<0,05). Sonuç olarak elde edilen veriler, histamin ve merkezi H1 reseptör antagonistinin uzun süreli tedavisinin, LH ve testosteron seviyeleri üzerinde inhibe edici etkilere sahip olduğunu göstermektedir. Bunun yanında, merkezi H2 ve H3/H4 reseptör antagonistleri ile yapılan kronik tedavinin üremenin düzenlenmesine katkı sağlayabileceği görülmektedir.

Anahtar Kelimeler

• Histamin
• Histamin antagonistleri
• merkezi sinir sistemi
• Hipotalamo-hipofizer-gonadal aks
• İntraserebroventriküler

The Effect of Chronically Intracerebroventricular Injected Histamine and Its Antagonists on the Hypothalamic-Pituitary-Axis

Öz

Histamine, which has neurotransmitter and neuromodulatory effects in the CNS, has a key role in regulating behavioral state, biological rhythm, body weight, energy metabolism, thermoregulation, fluid balance, stress, and reproduction. We have shown that acute central injections of histamine are effective in the hypothalamic-pituitary-gonadal (HPG) axis and that histamine central H1/H2 receptors mediate this effect. However, there is no explanatory information about the effects of long-term central treatments of histamine and histamine receptor antagonists in the HPG axis in studies. In the study, the effects of chronically intracerebroventricular (i.c.v.) injected histamine and its antagonists on plasma levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone hormone, which play a role in the HPG axis, were investigated. Studies were performed in male Sprague–Dawley rats. Histamine (100 nmol), histaminergic H1 receptor antagonist chlorpheniramine (100 nmol), H2 receptor antagonist ranitidine (100 nmol), or H3/H4 receptor antagonist thioperamide (100 nmol) was injected i.c.v. for 7 days. Chronic injection of histamine and its antagonists did not make a significant difference in plasma levels of GnRH. Chronic histamine or chlorpheniramine treatment increased plasma FSH levels (p<0,05) and decreased LH/testosterone levels (p<0,05). Chronic ranitidine or thioperamide treatment did not have an effect on plasma FSH levels but caused increases in LH and testosterone levels (p<0,05). The resulting data suggest that long-term treatment of histamine and central H1 receptor antagonist has inhibitory effects on LH and testosterone levels. Besides, it appears that chronic treatment with central H2, H3/H4 receptor antagonists can contribute to the regulation of reproduction.

Anahtar Kelimeler

• Histamine
• Histamine Antagonists
• Central Nervous System
• Hypothalamic-pituitary-gonadal axis
• Intraserebroventricular

Kaynakça

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