Alpha-subunit secretion in men with idiopathic hypogonadotropic hypogonadism

We studied the regulation of glycoprotein hormone alpha-subunit secretion in four men with idiopathic hypogonadotropic hypogonadism due to presumed GnRH deficiency. Immunoreactive alpha-subunit was present at low but usually detectable levels in blood samples drawn at 10- to 20-min intervals for 12-24 h; however, no characteristic pattern of pulsatile alpha-subunit secretion was found. Serum from each man was examined by gel filtration chromatography. Each sample tested contained an immunoreactive alpha-subunit peak with a slightly lower elution volume than [125I]hCG alpha, as we had previously found in serum from normal men. To determine if this peak represented TSH alpha, two men were treated with 0.3 mg L-T4 daily for 7-14 days. Serum TSH levels decreased to less than 1.5 mU/L, and neither TSH nor alpha-subunit levels increased after the iv administration of 500 micrograms TRH. An alpha-subunit peak that eluted before [125I]hCG alpha was again found in the serum of T4-treated men. We conclude that glycoprotein hormone alpha-subunit is present in the serum of men with idiopathic hypogonadotropic hypogonadism in whom TSH secretion is completely suppressed by L-T4. The gonadotrophs represent the most likely source of this alpha-subunit. The finding of more normal alpha-subunit than LH secretion in these men indicates that the production of the gonadotropin subunits is differentially regulated in man and supports the hypothesis that factors in addition to GnRH regulate alpha-subunit gene expression.