title: 17β-Oestradiol indirectly inhibits thyrotrophin-releasing hormone expression in the hypothalamic paraventricular nucleus of female rats and blunts thyroid axis response to cold exposure.
abstract: Energy expenditure and thermogenesis are regultated by thyroid and sex hormones. Several parameters of hypothalamic-pituitary-thyroid (HPT) axis function are modulated by 17β-oestradiol (E(2)) but its effects on thyrotrophin-releasing hormone (TRH) mRNA levels remain unknown. We evaluated, by in situ hybridisation and Northern bloting, TRH expression in the paraventricular nucleus of the hypothalamus (PVN) of cycling rats, 2 weeks-ovariectomised (OVX) and OVX animals injected s.c. during 1-4 days with E(2) (5, 50, 100 or 200 μg ⁄ kg) (OVX-E). Serum levels of E(2), thyroid-stimulating hormone (TSH), prolactin, corticosterone and triiodothyronine (T(3)) were quantified by radioimmunoassay. Increased serum E(2) levels were observed after 4 days injection of 50 μg ⁄ kg E(2) (to 68.5 ± 4.8 pg ⁄ ml) in OVX rats. PVN-TRH mRNA levels were slightly higher in OVX than in virgin females at dioestrous 1 or pro-oestrous, decreasing proportionally to increased serum E(2) levels. E(2) injections augmented serum T(3), prolactin, and corticosterone levels. Serum TSH levels augmented with 4 days 50 μg ⁄ kg E(2), but not with the higher doses that enhanced serum T(3) levels. Exposure to cold for 1 h resulted in marked HPT axis activation in OVX rats, increasing the levels of TRH mRNA along the rostro-caudal PVN areas, as well as serum TSH, T(3), corticosterone and prolactin levels. By contrast, no significant changes in any of these parameters were observed in cold-exposed OVX-E (50 μg ⁄ kg E(2)) rats. Very few PVN-TRHergic neurones expressed the oestrogen receptor type-α, suggesting that the effects of E(2) on PVN-TRH expression are indirect, most probably as a result of its multiple modulatory effects on circulating hormones and their receptor sensitivity. The blunted response of OVX-E rats to cold coincides with the effects of E(2) on the autonomic nervous system and increased cold tolerance.
authors.affiliation: Departamento de Genética y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, México.
authors.forename: R M
authors.initials: RM
authors.lastname: Uribe
authors.forename: M
authors.initials: M
authors.lastname: Zacarias
authors.forename: G
authors.initials: G
authors.lastname: Corkidi
authors.forename: M
authors.initials: M
authors.lastname: Cisneros
authors.forename: J-L
authors.initials: JL
authors.lastname: Charli
authors.forename: P
authors.initials: P
authors.lastname: Joseph-Bravo
mesh_terms: D000818:Animals; D001835:Body Weight; D003080:Cold Temperature; D003345:Corticosterone / Q000097:blood; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010052:Ovariectomy; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism*; D011388:Prolactin / Q000097:blood / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000097:blood / Q000235:genetics
chemical_list: D047628:Estrogen Receptor alpha; D014284:Triiodothyronine; D004958:Estradiol; D013973:Thyrotropin-Releasing Hormone; D011388:Prolactin; D003345:Corticosterone