Discordant changes in pituitary concentrations of LH and TSH subunits following hormonal manipulation

Abstract

We have recently shown that mouse pituitary concentrations of free TSH-β and α-subunits respond divergently to thyroid hormone manipulations in vivo. This study contrasts the changes in free LH-β and α-subunits after castration and polyestradiol phosphate (E 2) administration with those in free TSH-β and α-subunits after thyroidectomy and thyroxine (T 4) administration. Target hormone depletion (castration or thyroidectomy) resulted in an increase in plasma concentrations of the respective tropic hormones and their subunits; target hormone administration (E 2 or T 4) resulted in a decrease in plasma concentrations. In contrast, pituitary subunit concentrations of LH and TSH responded discordantly to target hormone depletion or administration, and the nature of the discordance for α-subunit and LH-β was opposite to that for α-subunit and TSH-β. Hypogonadism caused a decrease in pituitary LH and LH-β concentrations to 65% ( P < 0.01) and 48% ( P < 0.001) of values in control (eugonadal) mice, respectively, while α-subunit was unchanged. Hypothyroidism caused a two-fold ( P < 0.001) and 20-fold ( P < 0.001) increase in pituitary TSH and TSH-β concentrations, respectively, while α-subunit fell to 68% ( P < 0.01) of values in control (euthyroid) mice. Administration of E 2 to hypogonadal mice resulted in a two-fold increase in pituitary LH and LH-β after 11 days, while α-subunit fell to 55% ( P < 0.01) of values in control (untreated hypogonadal) mice. Administration of T 4 to hypothyroid mice resulted in a fall after 12 and 33 days in pituitary TSH to 70% and 2% ( P < 0.001), and TSH-β to 16% ( P < 0.01) and 2% ( P < 0.001) of values in control (untreated hypothyroid) mice, respectively. In contrast, α-subunit concentrations were two-fold higher than controls after 12 days ( P < 0.01) and no different from controls after 33 days. During E 2 treatment of hypogonadal mice, the α-subunit/LH-β ratio decreased over 11 days to 30% of initial values ( P < 0.01). In contrast, during T 4 treatment of hypothyroid mice, the α-subunit/TSH-β ratio increased 11-fold ( P < 0.01) over 12 days. These discordant responses after hormone manipulation of LH-β and α-subunit, and TSH-β and α-subunit, and the different responses of a α-subunit relative to the respective β-subunit, suggest that the regulation of the synthesis and secretion of glycoprotein hormone subunits is different in and between the gonadotrope and thyrotrope.