Endocrine Abstracts

Hypogonadotropic hypogonadism is a syndrome which may be manifested clinically by low sex steroids because of low (or inappropriately normal) gonadotropins. To date, more than 30 genes were reported as possible reason for this condition, but genetic basis is still unknown for ~60% of HH cases. Due to this fact we decided to analyze mRNA expression of several HH-related genes which can be found in leukocytes of peripheral blood: GNRHR and GNRH1 (which are necessary for adequate biological effect of GnRH); PROK2 and CHD7 (which are responsible for the migration of GnRH neurons), WDR11 and DUSP6 (which are involved in normal sexual development). A quantitative determination of mRNA expression of these genes were comlpeted in the fresh peripheral blood sample by PCR in real time.

Examined patients: Ten women with hypogonadotropic hypogonadism (age from 18 to 53 y.o.); 4 of them suffer from 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.

Results: 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 anamnestic factors; but some affinities were found among patients who suffer from primary amenorrhea. 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.