Gonadotrophin-releasing hormone (GnRH) receptors are expressed in tissuesthat are not associated with reproduction e.g. cerebellum, heart.  Furthermore, there is evidence of cross talk between the reproductive and thyroid axes (e.g. re-seasonality).  This study reports effects of GnRH agonist (GnRHa) treatment (prior to puberty until early adulthood) on thyroid structure and functional markers in an ovine model.

Treated animals (male n=24, female n=21) received subcutaneous Goserelin-Acetate implants (Zoladex 3.6mg) every 4 wks from 8 (males), 28 (females) wks of age i.e. prior to puberty. Control (C) animals (males n=22, females n=21) received no hormonal treatment. Animals were euthanized at ~one year of age; thyroid glands were excised, weighed, PFA-fixed and paraffin embedded. 5µm sections were cut and immunocytochemically stained for Ki67 (marker of cellular differentiation) and the sodium-iodide symporter (NIS).

In both sexes, GnRHa treatment did not affect thyroid gland weight (males C 3.53±0.22g GnRHa 3.45±0.25g; females C 2.92±0.2, GnRHa 3.02±0.21) or the density of thyroid follicles. Quantification of follicle size distribution (6 images/animal) indicated a significant reduction in the proportion of very small follicles and an increase in small/medium sized follicles in GnRHa treated males and females, relative to controls.  GnRHa treatment was associated with a significant (P<0.05) decrease in the number of Ki-67 immunopositive cells in both sexes.  While there was also a significant decrease in NIS immunopositive cells in the GnRHa females, relative to controls, this difference was not seen in the males. These results suggest that chronic GnRHa treatment to block puberty alters both thyroid structure and function and supports a growing body of evidence that GnRH has effects on the physiology of body systems outwith the reproductive axis. 

Down regulation of GnRH action, for medical reasons (humans) or use as a contraceptive (zoos) may significantly affect the thyroid axis.