The Effect of a Novel Small Molecule Estradiol Guanidine Derivative on the Ovary and Uterus of Female Mice

In this study, a novel small molecule estradiol guanidine derivative (Guanidoestradiol, GDT) for female reproductive system targeting and nitric oxide (NO) release has been constructed by conjugating 17 beta-estradiol and L-arginine through an esterification reaction. After intraperitoneal administration in female mice, the serum Griess assay and immunohistochemical analysis of ovary and uterus were performed. GDT effectively increased NO concentration in the blood and produced some bio-effects that are beneficial to the reproductive system. The specific advantages are as follows: (1) the introduction of guanidine groups and amino groups improves the water solubility and bioavailability of estradiol and is expected to exert other biofunctions; (2) the estradiol residue of GDT gives the NO donor the ability for ovarian and uterine targeting; (3) combined administration of estradiol and NO to the uterus and ovary promoted endometrial thickening and expression of vascular proliferation markers; (4) the abundance of iNOS in tissues was reduced after treatment with NO donors. We suggest that Guanidoestradiol is a promising small-molecule drug to enhance normal endometrial and ovarian function and may play a role in promoting reproduction.