Hot flushes are due to the lack of estrogens and are the most characteristic climacteric complaints. Hormone replacement therapy was the standard treatment but now its use is limited because of side effects. Need therefore arises to search for non-estrogenic alternatives. The molting hormone 20-beta-hydroxyecdysone (Ecd) is produced by several plants including spinach and has no estrogenic or androgenic properties but enhances GABAergic effects in neurons. Since GABAergic compounds can ameliorate hot flushes, we investigated the effects of Ecd on subcutaneous body temperature of intact and ovariectomized (ovx) rats. The subcutaneous body temperature was recorded at 5-min intervals over a period of 3 hours. Rats were then ovx, and skin temperatures were recorded after an acute intravenous (5 mg) and during subchronic and chronic oral application of Ecd (73 mg/animal/day). For additional control purposes, a group of ovx rats received food containing estradiol-17β (E2). Skin temperature in individual ovx animals fluctuated largely with peaks (hot flushes) occurring every 20–40 minutes. Following the i. v. treatment with Ecd, skin temperature dropped by more than 1 °C, an effect much larger than in the controls. One and two weeks later, hot flushes were only seen in ovx controls but not in intact, E2-, or Ecd-treated animals. As a consequence, E2 and Ecd intake significantly (p < 0.05) reduced the mean temperature in ovx rats during the various time points of the study. These results suggest that Ecd is efficient to prevent hot flushes in ovx rats.
Key words
ecdysone - hot flushes - ovariectomy - rats
References
1
Shanafelt T D, Barton D L, Adjei A A, Loprinzi C L.
Pathophysiology and treatment of hot flashes.
Mayo Clin Proc.
2002;
77
1207-1218
3
Jones G, Jones D, Teal P, Sapa A, Wozniak M.
The retinoid-X receptor ortholog, ultraspiracle, binds with nanomolar affinity to an endogenous morphogenetic ligand.
FEBS J.
2006;
273
4983-4996
4
Flugge G, Oertel W H, Wuttke W.
Evidence for estrogen-receptive GABAergic neurons in the preoptic/anterior hypothalamic area of the rat brain.
Neuroendocrinology.
1986;
43
1-5
6
Tataryn I V, Lomax P, Bajorek J G, Chesarek W, Meldrum D R, Judd H L.
Postmenopausal hot flushes: a disorder of thermoregulation.
Maturitas.
1980;
2
101-107
8
Loprinzi C L, Sloan J, Stearns V, Slack R, Iyengar M, Diekmann B, Kimmick G, Lovato J, Gordon P, Pandya K, Guttuso jr. T, Barton D, Novotny P.
Newer antidepressants and gabapentin for hot flashes: an individual patient pooled analysis.
J Clin Oncol.
2009;
27
2831-2837
9
Kapur P, Jarry H, Wuttke W, Pereira B M, Seidlova-Wuttke D.
Evaluation of the antiosteoporotic potential of Tinospora cordifolia in female rats.
Maturitas.
2008;
59
329-338
11
Bathori M, Toth N, Hunyadi A, Marki A, Zador E.
Phytoecdysteroids and anabolic-androgenic steroids–structure and effects on humans.
Curr Med Chem.
2008;
15
75-91
14
Nieva C, Spindler-Barth M, Spindler K D.
Impact of heterodimerization on intracellular localization of the ecdysteroid receptor (EcR).
Arch Insect Biochem Physiol.
2008;
68
40-48
15
Seidlova-Wuttke D, Christel D, Kapur P, Nguyen B T, Jarry H, Wuttke W.
Beta-ecdysone has bone protective but no estrogenic effects in ovariectomized rats.
Phytomedicine.
2010;
17
884-889
16
Tsujiyama S, Ujihara H, Ishihara K, Sasa M.
Potentiation of GABA-induced inhibition by 20-hydroxyecdysone, a neurosteroid, in cultured rat cortical neurons.
Jpn J Pharmacol.
1995;
68
133-136
17
Okada M, Ishihara K, Sasa M, Izumi R, Yajin K, Harada Y.
Enhancement of GABA-mediated inhibition of rat medial vestibular nucleus neurons by the neurosteroid 20-hydroxyecdysone.
Acta Otolaryngol.
1998;
118
11-16
21
Cosmi S, Pawlyk A C, Alfinito P D, Roman J, Zhou T, Deecher D C.
Simultaneous telemetric monitoring of tail-skin and core body temperature in a rat model of thermoregulatory dysfunction.
J Neurosci Methods.
2009;
178
270-275
22
Sipe K, Leventhal L, Burroughs K, Cosmi S, Johnston G H, Deecher D C.
Serotonin 2A receptors modulate tail-skin temperature in two rodent models of estrogen deficiency-related thermoregulatory dysfunction.
Brain Res.
2004;
1028
191-202
23
Berendsen H H, Weekers A H, Kloosterboer H J.
Effect of tibolone and raloxifene on the tail temperature of oestrogen-deficient rats.
Eur J Pharmacol.
2001;
419
47-54
24
Williams H, Dacks P A, Rance N E.
An improved method for recording tail skin temperature in the rat reveals changes during the estrous cycle and effects of ovarian steroids.
Endocrinology.
2010;
151
5389-5394
25
Williams H, Dacks P A, Rance N E.
An improved method for recording tail skin temperature in the rat reveals changes during the estrous cycle and effects of ovarian steroids.
Endocrinology.
2010;
151
5389-5394
26
Pawlyk A C, Cosmi S, Alfinito P D, Maswood N, Deecher D C.
Effects of the 5-HT2A antagonist mirtazapine in rat models of thermoregulation.
Brain Res.
2006;
1123
135-144
27
Kapur P, Wuttke W, Jarry H, Seidlova-Wuttke D.
Beneficial effects of beta-ecdysone on the joint, epiphyseal cartilage tissue and trabecular bone in ovariectomized rats.
Phytomedicine.
2010;
17
350-355
29
Mansky T, Mestres-Ventura P, Wuttke W.
Involvement of GABA in the feedback action of estradiol on gonadotropin and prolactin release: hypothalamic GABA and catecholamine turnover rates.
Brain Res.
1982;
231
353-364
30
Herbison A E, Chapman C, Dyer R G.
Role of medial preoptic GABA neurones in regulating luteinising hormone secretion in the ovariectomised rat.
Exp Brain Res.
1991;
87
345-352
