Trace Of Leuprolide Gonadal Axis Regulation In Female Rats

Leuprorelin acetate is a potent gonadotropin-releasing hormone agonist, which molecular formula is C59H84N16O12. It has a high affinity for gonadotropin-releasing hormone (GnRH) receptor. Leuprorelin acetate is used for the treatment of endocrinology, gynecology, pediatrics and certain tumors and other diseases in clinical, such as prostate cancer, benign prostatic hyperplasia, endometriosis, uterine fibroids, idiopathic precocious puberty, etc. In clinical, with high dose of Leuprorelin acetate repeatedly.Immediately after the first administration produced a transient pituitary-gonad system excitatory effects (acute effects), and then inhibit the production and release pituitary gonadotropin. It also further suppresses the ovaries and testes on the gonadotropin response, thereby reducing the formation of estradiol and testosterone (chronic effect).As GnRH analogues, leuprorelin acetate has strong activity. of GnRH. As the endocrine system in maintaining homeostasis, growth, development and aging is great significance, hypothalamic-pituitary-gonadal axis in the aging process of change is particularly prominent, as the senior nerve center of hypothalamic-pituitary-gonadal axis, it'si importance that hypothalamus effects the aging of hypothalamic-pituitary-gonadal axis. GnRH as a important hormone that is secreted by Hypothalamic neurons through Pulsed way.It can control the hypothalamic-pituitary-gonadal axis. The main physiological role for GnRH is to stimulate the pituitary to secretes follicle stimulating hormone (FSH) and luteotropic hormone (LH), In addition, it can also act directly on the ovary, affecting estrogen (E2) secretion. In the aging process, its secretion occurs certain disorders, which can affect the hypothalamic-pituitary-gonadal axis. Leuprorelin acetate as a GnRH agonist, has some role in the hypothalamic-pituitary-gonadal axis. In clinical, large dose can inhibite it, but how is a small dose of Leuprorelin acetate to hypothalamic-pituitary-gonadal axis? That micro-injection of long-term to the body of Leuprorelin acetate, whether can improve the function of hypothalamic-pituitary-gonadal axis recession caused by aging?In recent years, the study of leuprorelin acetate focused on the clinical treatment of hormone-dependent diseases, but the use of small doses remains to be studied further. Linked to influence of the GnRH to organism gonadal axis of the aging. There is the reports point the feasibility of GNRH against with aging. This experiment study out probing the influence of small dose leuprorelin acetate on the gonadal axis related hormones.In this experiment, female SD rats were studied by adopting HE staining, radioimmunoassay and immunohistochemistry. Through the contrast of the blank group without leuprorelin acetate and younger youth group, the research design three doses of drug group to study gonadal axis and estrogen receptor respectively. The main conclusions are as follows.1 The effect on the levels of Peripheral Blood's GnRH,E2,FSH and LH from leuprorelin acetateBy radioimmunoassay:The serum levels of GnRH of high dose group in rat were significantly lower than the control group, with statistical significance (P<0.05), low dose and middle dose group was lower than the control group, but no statistical significance, there is no significant difference between control group and the young control group. leuprorelin acetate may be competitively inhibit secretion of hypothalamic GnRH.The levels of E2 from all doses of group in blood were significantly higher than the control group, and higher than the young control group, there was significant (P <0.05), slight differences between each dose of group, but there is no statistically significant. It can be speculated that leuprorelin acetate can directly act on the ovary, affecting the secretion of E2.The levels of FSH and LH in rats of all groups were not significantly different, possibly atom of leuprorelin acetate has no significant effect on pituitary gonadotropin.2 The effect on ovarian morphology from leuprorelin acetateBy HE staining and observed under the microscope, the number of ovarian follicles in young control rats from all doses of groups are significant more than the other groups, possibly because that the young control group's age are older than other groups, and the developing follicles are more. The rats of each dose of group had higher ovarian follicles than the control group, while There were no significant difference between all dose of groups. May be the levels of E2 increased, promoting the development of follicles.The rats on the ovarian wet weight were measured, after statistics, each group had no There are no significant statistical difference between all groups.It could be due to the rats of the drug groups and control group did not reach the state of ovarian atrophy with aging.3 The effect of on ER expression in different tissues from leuprorelin acetateUsed immunohistochemistry to study expression of ERa and ERβon the rats'cerebral cortex,hippocampus CA1 area,hypothalamus and ovary, each dose of group was found in different parts of the two receptors was higher than that in control group, while the expression of the young control group comparing with all dose of groups and the control group, showed no consistency. It Can be drawn up leuprorelin acetate up regulate the ER expression may be related to the increased level of E2. In summary, in the aging process, used leuprorelin acetate of low doses than commonly, could improve ovarian function and enhance the level of E2, and could raise the expression of ER, indicating that it has acceleration on hypothalamic-pituitary-gonadal axis of female rat.for That provides some basis for the development of leuprorelin acetate on other purposes. But the specific mechanisms and experimental study on male animals have to be continued.