Prolactin and growth hormone stimulation of lactation in mice requires thyroid hormones

This experiment tested the hypothesis that thyroid hormones are essential f or a milk production response to growth hormone (GH) and prolactin (PRL), P rior to breeding, female transgenic mice expressing the herpes simplex type -I thymidine kinase in the thyroid were treated with ganciclovir to ablate thyroid follicular cells. To provide for normal gestation, thyrocyte-ablate d mice were supplied thyroxine (T-4) in drinking water (0.2 mu g/ml) until 7 days before parturition, Litter size was adjusted to 9 pups, hormone admi nistration began on Day 2 of lactation, and mice were sacrificed on Day 12, There were 5-6 mice in each of 7 treatments that included nonablated contr ols, thyrocyte-ablated controls, and thyrocyte-ablated mice treated with T- 4, GH, PRL, GH + T-4, and PRL + T-4. Thyroxine was administered in drinking water, and GH and PRL (20 mu g/d) were administered by subcutaneous inject ion. Compared with thyrocyte-ablated controls, litter weight gain was unaff ected when dams were treated with GH, PRL, or T-4 alone. However, when dams were treated with GH or PRL in combination with T-4, litter weight gain in creased 13% compared with thyrocyte-ablated controls and 18% compared with GH or PRL-treated mice. Concentration of T-4 in serum of pups averaged 62 n g/ml and did not differ among treatments. Concentration of T-4 in serum of dams averaged 76 ng/ml when T-4-treated. Thyroxine 5'-deiodinase (5'D), the enzyme that converts T-4 to triiodothyronine, was quantitated in liver, ki dney, and mammary gland, Quantity of 5'D was lower in liver and kidney of t hyrocyte-ablated dams without T-4 than in respective tissues of mice treate d with T-4, and there was no effect of GH or PRL. However, in mammary gland , 5'D was increased by treatment with GH, PRL, or T-4. Data show that thyro id hormones are necessary for a galactopoietic response to GH and PRL and d emonstrate a unique organ-specific regulation of 5'D by galactopoietic horm ones.