Thyroid hormone-binding inhibitor in normal, pregnant, and lactating rat and postmenopausal human breast tissue

The regulatory role of thyroid hormones in the synthesis of milk proteins and functional differentiation of the murine mammary gland has been demonstrated. Further, T4 and T3 and their metabolites are found in both rat and human milk. Since the enhanced metabolic demands of mammo- and lactogenesis may result in increased local hormonal requirements, we examined breast tissue from normal (virgin), pregnant, and lactating female rats, as well as postmenopausal human breast tissue for the presence of a thyroid hormone-binding inhibitor (THBI). This substance, which decreases binding of T4 to serum T4-binding globulin, has been described in rat liver, kidney, muscle, and intestine, and in the circulation of patients with nonthyroidal illnesses. THBI activity in the present study was assessed by equilibrium dialysis in whole tissue homogenates; the ether-soluble fraction was also analyzed for THBI activity by RIA. In a range of 0.8-8.0 mg tissue protein, we found lactating rat breast to contain elevated THBI levels when compared to those found in normal, virgin breast tissue. Half-maximum binding inhibition was achieved at 0.15 mg lactating breast tissue protein, vs. 0.23 mg breast tissue protein and 0.35 mg liver protein in homogenates from normal resting animals. Expressed in tissue milligram equivalents, half-maximum binding inhibition of lactating, 18-day pregnant, and normal rat breast tissue was 0.7, 2.6, and 4.8 mgeq, respectively. Thus, the THBI activity of lactating rat breast tissue was more than 3-fold greater than that of the pregnant rat and 7-fold greater than that found in resting breast tissue. Binding inhibition in postmenopausal human breast tissue was comparable to that of rat breast and liver tissue at low protein concentrations, but the maximum inhibition attainable (205 +/- 6%, n = 3) was significantly lower than that achieved by normal rat breast tissue (338 +/- 6%, n = 6; means +/- SEM). The ether-soluble fraction of breast tissue homogenates was also analyzed employing a THBI-RIA. THBI activity, expressed as percent binding inhibition, was elevated in extracts from lactating rat breast tissue in comparison to tissue from pregnant or normal animals at 6.0, 12.5, and 25 mgeq; the largest differences were observed at 25 mgeq tissue: lactating (57.8 +/- 2.3%) vs. pregnant (46.5 +/- 3.1%, P less than 0.01) vs. normal (41.7 +/- 2.3%, P greater than 0.05); n = 3 in all cases.(ABSTRACT TRUNCATED AT 400 WORDS)