Studies on the Mechanism by which Thyroid Hormones Enhance α-Lactalbumin Activity in Explants from Mouse Mammary Glands

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Abstract
Addition of 3,5,3''-triiodo-L-thyronine to cultures of [mouse] mammary gland explants in serum-free medium containing [porcine] insulin, hydrocortisone and prolactin results in a 3 to 5-fold increase in the activity of the milk-protein .alpha.-lactalbumin over that seen in the presence of the latter 3 hormones alone. The thyroid hormone does not act by substituting for any of the other hormones. It need not be present throughout the culture period but can act if added along with prolactin after insulin and hydrocortisone have induced formation of the rough endoplasmic reticulum. Delayed addition of the thyroid hormone further stimulates cells already responding maximally to insulin, hydrocortisone and prolactin. These effects of triiodothyronine [T3] are not blocked by progesterone at 1 .mu.g per ml. They are blocked by the addition of inhibitors of RNA (actinomycin D) or protein (cycloheximide or puromycin) synthesis, suggesting that the thyroid hormone increases the synthesis of the .alpha.-lactalbumin molecule itself. The thyroid hormone appears to act by altering the responsiveness of the mammary gland explants to prolactin, but not to insulin or hydrocortisone. In the presence of 10-9 M T3, the enhanced .alpha.-lactalbumin activity is consistently obtained at prolactin concentrations as low as 4.5 .times. 10-12 M whereas, in the absence of the thyroid hormone, 10 times more prolactin (4.5 .times. 10-11 M) is needed to obtain an increase in .alpha.-lactalbumin activity.