Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue.
Dysfunction in thyroid regulation can cause menstrual and ovulatory disturbances, the mechanism of which is not clear. The distribution and activity of the thyroid-stimulating hormone (TSHR), and the thyroid hormone receptors (TR) alpha1, alpha2 and beta1 in human ovarian tissue and in granulosa cells was studied using immunohistochemistry, reverse-transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and immunoassays. Strong immunostaining of TSHR, TRalpha1 and TRbeta1 was observed in ovarian surface epithelium and in oocytes of primordial, primary and secondary follicles, with minimal staining in granulosa cells of secondary follicles. Granulosa cells of antral follicles expressed TSHR, TRalpha1 and TRbeta1 proteins. Messenger RNA for all receptors was present in ovarian tissue. Mature human granulosa cells expressed transcripts for 5' deiodinases types 2 and 3, but not type 1, indicating the possibility of conversion of peripheral thyroid hormone thyroxin (T(4)). Granulosa cells stimulated with TSH showed a significant increase in cAMP concentrations after 2 h of culture (P = 0.047), indicating activation through TSHR. Stimulation with T(4) resulted in increased extracellular signal-regulated kinase 1 and 2 activation after 10, 30, 60 min and 24 h. These data demonstrate that TSH and thyroid hormone receptors may participate in the regulation of ovarian function.
Aghajanova
Lusine
L
Department of Clinical Science, Intervention and Technology, Division of Obstetrics and Gynaecology, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden. aghajanoval@obgyn.ucsf.edu
Lindeberg
Maria
M
Carlsson
Inger Britt
IB
Stavreus-Evers
Anneli
A
Zhang
Pu
P
Scott
Jennifer E
JE
Hovatta
Outi
O
Skjöldebrand-Sparre
Lottie
L
D000328:Adult; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D010053:Ovary / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013972:Thyrotropin / Q000502:physiology; D013974:Thyroxine / Q000502:physiology
D017931:DNA Primers; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D013974:Thyroxine