Receptors for thyrotropin-releasing hormone, thyroid-stimulating hormone, and thyroid hormones in the macaque uterus:  effects of long-term sex hormone treatment.
OBJECTIVE
Thyroid gland dysfunction is associated with menstrual cycle disturbances, infertility, and increased risk of miscarriage, but the mechanisms are poorly understood. However, little is known about the regulation of these receptors in the uterus. The aim of this study was to determine the effects of long-term treatment with steroid hormones on the expression, distribution, and regulation of the receptors for thyrotropin-releasing hormone (TRHR) and thyroid-stimulating hormone (TSHR), thyroid hormone receptor α1/α2 (THRα1/α2), and THRβ1 in the uterus of surgically menopausal monkeys.


METHODS
Eighty-eight cynomolgus macaques were ovariectomized and treated orally with conjugated equine estrogens (CEE; n = 20), a combination of CEE and medroxyprogesterone acetate (MPA; n = 20), or tibolone (n = 28) for 2 years. The control group (OvxC; n = 20) received no treatment. Immunohistochemistry was used to evaluate the protein expression and distribution of the receptors in luminal epithelium, glands, stroma, and myometrium of the uterus.


RESULTS
Immunostaining of TRHR, TSHR, and THRs was detected in all uterine compartments. Epithelial immunostaining of TRHR was down-regulated in the CEE + MPA group, whereas in stroma, both TRHR and TSHR were increased by CEE + MPA treatment as compared with OvxC. TRHR immunoreactivity was up-regulated, but THRα and THRβ were down-regulated, in the myometrium of the CEE and CEE + MPA groups. The thyroid-stimulating hormone level was higher in the CEE and tibolone groups as compared with OvxC, but the level of free thyroxin did not differ between groups.


CONCLUSIONS
All receptors involved in thyroid hormone function are expressed in monkey uterus, and they are all regulated by long-term steroid hormone treatment. These findings suggest that there is a possibility of direct actions of thyroid hormones, thyroid-stimulating hormone and thyrotropin-releasing hormone on uterine function.
Division for Reproductive Endocrinology, Department of Women's and Children's Health, Karolinska Institutet, Solna, Stockholm, Sweden.
Mariana
M
Hulchiy
Hua
H
Zhang
J Mark
JM
Cline
Angelica Lindén
AL
Hirschberg
Lena
L
Sahlin
D000818:Animals; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000662:veterinary; D008252:Macaca fascicularis; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D009652:Norpregnenes / Q000008:administration & dosage; D011988:Receptors, Thyroid Hormone / Q000032:analysis / Q000187:drug effects*; D011989:Receptors, Thyrotropin / Q000032:analysis / Q000187:drug effects*; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000032:analysis / Q000187:drug effects*; D037021:Thyroid Hormone Receptors alpha / Q000032:analysis / Q000187:drug effects; D037042:Thyroid Hormone Receptors beta / Q000032:analysis / Q000187:drug effects; D014599:Uterus / Q000737:chemistry* / Q000502:physiology
D004966:Estrogens, Conjugated (USP); D012739:Gonadal Steroid Hormones; D009652:Norpregnenes; D011988:Receptors, Thyroid Hormone; D011989:Receptors, Thyrotropin; D018025:Receptors, Thyrotropin-Releasing Hormone; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D017258:Medroxyprogesterone Acetate; C027385:tibolone