Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta

Abstract

Objective: Some phytoestrogens are believed to have selective estrogen receptor modulator (SERM) activity with no action in the uterus but beneficial effects in the hypothalamo/pituitary unit and in the bone and are presently the focus of clinical interest. In the present experiments, the effects of the clinically used Cimicifuga racemosa (CR) extract BNO 1055 in the uterus, in the bone and on serum luteinizing hormone (LH) were compared with the effects of estradiol-17b (E 2 ) under acute and chronic conditions in ovariectomized rats. Methods: Ovariectomized rats were treated either acutely (6 h) or chronically (3 months) with E 2 or the CR extract. Gene expression of some estrogen-regulated genes in the metaphysis of the tibia and the uterus was determined. Furthermore, bone mineral density was measured by quantitative computer tomography. Results: When given acutely, both E 2 and the CR extract inhibited LH secretion and slightly stimulated gene expression of IGF-I, collagen-1a1, osteoprotegerin and osteocalcin (all osteoblast products), and of tartrate-resistant acid phosphatase (TRAP, an osteoclast product) in the metaphysis of the femur. While E 2 stimulated uterine weight and expression of progesterone receptor (PR), the complement protein (C3) and IGF-I genes, and inhibited gene expression of the estrogen receptor b (ERb) in the uterus, no such effect was observed under acute CR treatment. After chronic application with pelleted food over 3 months E 2 had profound effects in the uterus on weight and gene expression (ERb, PR, C3 and IGF-I) which were not seen in the CR-treated animals. Within 3 months after ovariectomy, control rats had lost more than 50% of the metaphyseal bone mass of the tibia, an effect prevented by E 2 and partially by CR supplementation.

Effects of 8-prenylnaringenin on the hypothalamo-pituitary-uterine axis in rats after 3-month treatment

“…Extraction of total RNA from the organs or micropunches of the POA of the hypothalamus and the protocol of the real-time PCR were described in detail previously (Roth et al 2001a, Seidlova-Wuttke et al 2003c. The reactions were run on an ABI Prism 7700 Sequence Detection System (TaqMan; PE Applied Biosystems, Foster City, CA, USA).…”

“…The reactions were run on an ABI Prism 7700 Sequence Detection System (TaqMan; PE Applied Biosystems, Foster City, CA, USA). The primers and probes were synthesized according to published validated systems: ER and ER , IGF-I, C3 and PR (Seidlova-Wuttke et al 2003c); GnRH and its receptor (Roth et al 2001b). Oligonucleotides were purchased from Eurogentec (Seraing, Belgium).…”

Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats

“…Treatment of ovariectomized (OVX) women or rats with E2 dampens the activity of the GnRH pulse generator, resulting in reduced pituitary luteinizing hormone (LH) secretion and diminishing or ceasing hot flushes. Thus, the negative feedback action of E2 or substances with estrogenic activity on LH secretion can be used as an indirect measure of the potency to ameliorate hot flush activity (Seidlova-Wuttke et al 2003b). …”

Black cohosh (Cimicifuga racemosa) is a non-estrogenic alternative to hormone replacement therapy

“…Ovariectomy of rats results in the typical pulsatile LH release (Fig. 7a, b) also seen in postmenopausal women whereas estradiol inhibits it [58]. Fig.…”