Cryptotanshinone reverses reproductive and metabolic disturbances in prenatally androgenized rats via regulation of ovarian signaling mechanisms and androgen synthesis

Abstract

reverses reproductive and metabolic disturbances in prenatally androgenized rats via regulation of ovarian signaling mechanisms and androgen synthesis. Am J Physiol Regul Integr Comp Physiol 300: R869 -R875, 2011. First published January 12, 2011 doi:10.1152/ajpregu.00334.2010.-This trial explores 1) prenatally androgenized (PNA) rats as a model of polycystic ovary syndrome (PCOS) and 2) reproductive and metabolic effects of cryptotanshinone in PNA ovaries. On days 16 -18 of pregnancy, 10 rats were injected with testosterone propionate (PNA mothers) and 10 with sesame oil (control mothers). At age 3 mo, 12 female offspring from each group were randomly assigned to receive saline and 12 cryptotanshinone treatment during 2 wk. Before treatment, compared with the 24 controls, the 24 PNA rats had 1) disrupted estrous cycles, 2) higher 17-hydroxyprogesterone (P ϭ 0.030), androstenedione (P ϭ 0.016), testosterone and insulin (P values ϭ 0.000), and glucose (P ϭ 0.047) levels, and 3) higher areas under the curve (AUC) for glucose (AUC-Glu, P ϭ 0.025) and homeostatic model assessment for insulin resistance (HOMA-IR, P ϭ 0.008). After treatment, compared with vehicle-treated PNA rats, cryptotanshinone-treated PNA rats had 1) improved estrous cycles (P ϭ 0.045), 2) reduced 17-hydroxyprogesterone (P ϭ 0.041), androstenedione (P ϭ 0.038), testosterone (P ϭ 0.003), glucose (P ϭ 0.036), and insulin (P ϭ 0.041) levels, and 3) lower AUC-Glu (P ϭ 0.045) and HOMA-IR (P ϭ 0.024). Western blot showed that cryptotanshinone reversed the altered protein expressions of insulin receptor substrate-1 and -2, phosphatidylinositol 3-kinase p85␣, glucose transporter-4, ERK-1, and 17␣-hydroxylase within PNA ovaries. We conclude that PNA model rats exhibit reproductive and metabolic phenotypes of human PCOS and that regulation of key molecules in insulin signaling and androgen synthesis within PNA ovaries may explain cryptotanshinone's therapeutic effects.

Genome-wide identification of aberrantly methylated promoters in ovarian tissue of prenatally androgenized rats

“…Plasma T levels increased twofold in T-injected rats compared with in controls. We built a PNA rat model by injecting rats SC with 2.5 mg/day T propionate on days 16, 17, and 18 of pregnancy (based on our previous study) (20). The pregnant women with PCOS exhibited significantly higher concentrations of T, A, and DHEAS than normal pregnant women.…”

“…Pregnant female rats were randomized into two groups. On days 16, 17, and 18 of pregnancy, 10 females were injected SC with 2.5 mg/day T propionate (2.5 mg/mL, Shanghai GM, purchased from the Affiliated Hospital, Heilongjiang University of Chinese Medicine) according to our previous study (20). On days 16, 17, and 18 of pregnancy, 10 females were injected SC with 0.1 mL neutral tea oil daily.…”

Tanshinones: Sources, Pharmacokinetics and Anti-Cancer Activities

“…Li et al [266] reported that CT (27 mg/kg of CT in Tween 80/saline, oral gavage for 14 days) decreased plasma 17α-hydroxy progesterone in male offspring with high circulatory androgen stimulated by prenatal androgenization. Similarly, Yang et al [267] reported that CT (27 mg/kg, 14 day) attenuated the increased plasma androgen level in female offspring receiving prenatal androgenization, in association with reduction of androgen synthesis enzyme CYP17. Zhao et al [268] reported that CT (600 mg/kg of CT, oral gavage for 8 weeks) reversed the increased plasma testosterone level caused by Akt2 deletion in mice, in association with decrease of CYP17.…”

The physiological basis of complementary and alternative medicines for polycystic ovary syndrome

“…Other CHMs, such as Radix notoginseng, have been found to have similar antidiabetic effects in mouse models, improving not only glucose tolerance and insulin action in a dose-response fashion but also ameliorating obesity (13). Similarly, Salvia miltiorrhiza Bunge has been shown to significantly improve glucose tolerance in a prenatally androgenized rat model of PCOS and to favorably impact insulin signaling in treated animals (118). Berberine, a component of Rhizoma coptidis, has been shown to improve glucose uptake and insuln action in human thecal cells with dexamethasone-induced insulin resistance (125).…”