RSS-Feed abonnieren
DOI: 10.1055/s-0031-1280317
© Georg Thieme Verlag KG Stuttgart · New York
20-OH-Ecdysone Prevents Hot Flushes in Ovariectomized Rats
Publikationsverlauf
received April 5, 2011
revised October 6, 2011
accepted October 9, 2011
Publikationsdatum:
14. November 2011 (online)

Abstract
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
Reference Ris Wihthout Link
- 2
Rossouw J E.
Effect of postmenopausal hormone therapy on cardiovascular risk.
J Hypertens.
2002;
20
(Suppl)
S62-S65
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 5
Smith M J, Jennes L.
Neural signals that regulate GnRH neurones directly during the oestrous cycle.
Reproduction.
2001;
122
1-10
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 7
Sturdee D W.
The menopausal hot flush – anything new?.
Maturitas.
2008;
60
42-49
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 10
Butenandt A, Karlson P.
Über die Isolierung eines Metamorphosehormones der Insekten in kristallieiserter Form.
Z Naturforsch.
1954;
9
389-391
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 12
Seidlova-Wuttke D, Ehrhardt C, Wuttke W.
Metabolic effects of 20-OH-ecdysone in ovariectomized rats.
J Steroid Biochem Mol Biol.
2010;
119
121-126
Reference Ris Wihthout Link
- 13
Dinan L, Lafont R.
Effects and applications of arthropod steroid hormones (ecdysteroids) in mammals.
J Endocrinol.
2006;
191
1-8
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 18
Chaudhary K D, Lupien P J, Hinse C.
Effect of ecdysone on glutamic decarboxylase in rat brain.
Experientia.
1969;
25
250-251
Reference Ris Wihthout Link
- 19
Seidlova-Wuttke D, Hesse O, Jarry H, Christoffel V, Spengler B, Becker T, Wuttke W.
Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta.
Eur J Endocrinol.
2003;
149
351-362
Reference Ris Wihthout Link
- 20
Seidlova-Wuttke D, Ehrhardt C, Wuttke W.
Metabolic effects of 20-OH-ecdysone in ovariectomized rats.
J Steroid Biochem Mol Biol.
2010;
119
121-126
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 28
Freedman R R.
Pathophysiology and treatment of menopausal hot flashes.
Semin Reprod Med.
2005;
23
117-125
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
- 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
Reference Ris Wihthout Link
Prof. Dr. Wolfgang Wuttke
Department of Endocrinology
University Medical Center Göttingen
Robert-Koch-Strasse 40
37099 Göttingen
Germany
Telefon: +49 5 51 39 67 14
Fax: +49 5 51 39 65 18
eMail: ufkendo@med.uni-goettingen.de