Inhibitory effect of dihydrotestosterone on human thyroid cell growth.
Sex steroid-binding activities have been identified by several authors in normal and pathological thyroids and the expression of the canonic androgen receptor (AR) has recently been demonstrated in human thyroid follicular cells. In order to assess what influence, if any, androgen exposure has on thyroid cell growth, the effect of dihydrotestosterone (DHT) on [3H]thymidine (thy) incorporation and cell proliferation was investigated in thyroid follicular cells in vitro. In a primary culture of goitrous cells, DHT induced a significant reduction of [3H]thy incorporation at concentrations ranging from 10(-12) to 10(-8) M, with a more pronounced effect at 10(-9) M. At this concentration, the inhibitory effect was evident after both 24 and 48 h of treatment and in various types of primary thyroid cell cultures. In goitrous cells, the DHT-induced decrease of [3H]thy was associated with a reduction of expression of the proliferation-associated nuclear Ki-67 antigen, a protein commonly used to assess cell growth fraction. In TPC cells, an AR-positive thyroid papillary carcinoma cell line, DHT at concentrations between 10(-12) and 10(-8) M significantly decreased the growth rate. DHT (10(-9) M) produced an approximately 50-60% inhibition of cell proliferation and the antiandrogen cyproterone acetate was capable of reversing such effects. The DHT-induced reduction of TPC cell proliferation was associated with a significant reduction of c-myc RNA levels. Thyroperoxidase mRNA levels and thyroglobulin production were not reduced by androgen in primary cultures of goitrous cells. In conclusion, our results indicated that androgens may have a role in this gland by reducing the proliferation, but not the function, of follicular cells.
Rossi
R
R
Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi, Ferrara, Italy.
Zatelli
M C
MC
Franceschetti
P
P
Maestri
I
I
Magri
E
E
Aguiari
G
G
Cavazzini
P
P
degli Uberti
E C
EC
del Senno
L
L
D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D006042:Goiter / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D012313:RNA / Q000032:analysis; D011944:Receptors, Androgen / Q000032:analysis; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D019394:Ki-67 Antigen; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D012313:RNA; D013936:Thymidine