Физиологическое действие гипоталамо-гипо-физарно-гонадной оси основывается на пульсиру-ющей гипоталамической секреции гонадолиберина (ГнРГ), нарушение которой является причиной ред-ких заболеваний, объединяемых под термином ги-погонадизм. Отсутствие ГнРГ приводит к дезакти-вации рецептора на поверхности гонадотрофов аде-ногипофиза и выпадению стимулирующего дей-ствия на синтез и высвобождение гонадотропинов (ЛГ и ФСГ) в общий кровоток. Дефицит ЛГ и ФСГ обусловливает отсутствие гаметогенеза и синтеза половых стероидов. Таким образом, нормальное функционирование репродуктивной системы зави-сит от скоординированной работы трех звеньев: ар-куатных ядер гипоталамуса, гонадотрофов гипофиза и гонад (рис. 1).В зависимости от сроков возникновения разли-чают врожденный и приобретенный гипогонадизм, а в зависимости от уровня поражения -первичный (поражение самих гонад) и вторичный (гипоталамо-гипофизарный) гипогонадизм. Существует также классификация, разделяющая поражения гипофиза и гипоталамуса на вторичный и третичный уровень
Background. Hypogonadotropic hypogonadism (HH) is a disorder characterized by delayed or absent pubertal development due to pathology of the hypothalamic-pituitary-gonadal axis. HH may be both congenital (Kallmann’s syndrome) and sporadic. Congenital or isolated HH is divided into with anosmia/hyposmia (KS) and with normal olfaction (nIHH). Nowadays several tens of genes involved in the functioning of the reproductive axis are known. However DNA lesions can be found just in 5-15% of such cases of HH.Aim. So we decided to measure mRNA expression of several genes which can be found in leukocytes of peripheral blood - namely GNRHR and GNRH1 (are necessary for adequate biological effect of GnRH); PROK2 and CHD7 (are responsible for the migration of GnRH neurons), WDR11 and DUSP6 (are involved in normal sexual development).Methods. A quantitative determination of mRNA expression of these genes were comlpeted in the fresh peripheral blood sample by PCR in real time.Results. Examined patients: 9 women with hypogonadotropic hypogonadism (age from 18 to 28 y.o.); duration of the disease from 2 to 15 years; 3 of them – amenorrhea I and 6 – amenorrhea II. Reasons of amenorrhea II were: stress, excessive exercises, rapid body weight loss, past use of oral contraceptives. The control group: 19 healthy women; age from 19 to 37 y.o.; with regular ovalutory menstrual cycle, some of them have children. mRNA expression of examined genes differed from normal patterns in each case of hypogonadotropic hypogonadism. Changes in GNRHR, GNRH1 and DUSP6 mRNA expression were found in most of cases. However variations of mRNA expression were multidirectional in each case and there was no similarity among expression profiles of patients according to amenorrhea type or anamnestic factors.Conclusions. According to our preliminary results, in women with hypogonadotropic hypogonadism the functional activity damage of “reproductive-responsible” genes could be found in each case. Probably mRNA expression measuring could be a perspective method for proving hypothalamo-pituitary level of reproductive disorders and may help to determine which genes should be tested for DNA impairment.
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