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Adrenal and Thyroid Hormones

Adrenal and
Thyroid Hormones

Cows walking to the barn.

Adrenal Corticoids

*** are essential for maintenance of lactation.

Adrenal glucocorticoids can inhibit lactation at high doses. However, at lower doses (more physiological) exogenous glucocorticoid stimulates milk yield in rats in early lactation and prevents the expected decline in milk yield in later lactation. In ruminants, the effects of high doses of glucocorticoid is inhibitory, but the effects of lower doses are ambiguous, depending on the study evaluated.

In the adrenalectomized rat, milk secretion is impaired and casein mRNA levels are decreased by 85-92%. Cortisol administration will reverse this. Adrenalectomy-ovariectomy stops lactation completely.

In the rat, adrenal secretions are limiting. ACTH in the pituitary declines 68% during extended lactation. Adrenal corticosterone content also declines, but blood concentrations are unchanged. Adrenal corticoid content is highly correlated with mammary nucleic acid content during lactation. Corticoid binding globulin (CBG) declines in blood during early lactation, then increases during later lactation. So, even though blood corticoids stay the same during lactation, the effective concentration declines.

In cattle, there is no change in CBG during lactation. Corticoids are not limiting to milk yield in cows, but are nevertheless essential.

Thyroid Hormones

*** are essential for maximal secretion of milk.

Several observations on the role of thyroid hormone in maintenance of lactation:

  • Thyroidectomy can be achieved by surgical procedures or by irradiating the thyroid by ingesting radioactive iodine which is sequestered into the thyroid and essentially destroys the thyroid function. Thyroidectomy in cattle by either method results in decreased milk yield.
  • Injection of thyroid hormone into cattle for 7 weeks at 25% above the normal thyroid secretion rate results in increase milk yield by 27%. However, this is not a permanent effect because continued thyroid hormone administration at 150% for 7 more weeks. had little or no effect.
  • Feeding thyroprotein (iodinated casein) to cows increases milk yield by 10 % in early lactation and by 15-20% in late lactation. But, the effect only lasts 2-4 mos. and subsequent yields are below normal. There generally is no net benefit in feeding thyroprotein over the entire lactation. The transient increase in milk yield in cows fed thyroprotein feeding in cows only occurs when feed intake is increased.

Dairy cattle are under very high metabolic demands in early lactation. In addition, there is an inverse relationship between a cow's milk yield and blood levels of thyroid hormones in early lactation. Curiously, this apparent hypothyroid state of the cow is in contrast with the increased milk yield attained when lactating cows are administered thyroid hormone. This apparent inconsistency becomes clearer if the metabolism of thyroid hormones by non-thyroid tissues, including the mammary gland, is taken into account.

Mechanisms of thyroid hormone action:

Thyroid stimulating hormone is secreted by the anterior pituitary and stimulates secretion of thyroid hormones from the thyroid gland. The primary thyroid hormone produced in the thyroid gland is thyroxine (3,5,3',5'-tetraiodothyronine; or T4). The T4 is an alanine molecule with a tyrosyl ring and a phenolic ring, each of which is iodinated at the 3 and 5 and 3' and 5' carbon positions, respectively. However, T4 has a relatively low affinity for thyroid hormone receptors in target tissues and is considered a prohormone requiring further modification to achieve full activity. The major biologically active form of thyroid hormone is T3 (3,5,3'-tri-iodothyronine). Deiodination of T4 can occur in the thyroid gland or it can occur in the various target tissues. Several specific deiodinase enzymes have been identified, each belonging to a family of selenocysteine-containing enzymes. Type I deiodinase is found predominantly in the liver, kidney and thyroid, but is also present in skeletal muscle, heart, lung, intestine and mammary gland, at least in the rat. Type I deiodinase can catalyze either 5'- or 5-monodeiodination. The 5'-deiodination removes an iodine from the outer phenolic ring, resulting in formation of the active T3 (3,5,3'-tri-iodothyronine), while 5-deiodination removes an iodine from the inner tyrosyl ring, resulting in the inactive reverse T3 (3,3',5'-tri-iodothyronine). Type II deiodinase is found in the central nervous system (cerebral cortex, cerebellum, hypothalamus), pituitary, and brown adipose tissue. Type II deiodinase catalyzes only removal of the 5'-iodine. Therefore, type II deiodinase will convert T4 to T3, while rT3 is converted to the inactive T2 (3,3'-di-iodothyronine). Type III deiodinase has 5-deiodinase activity and therefore converts active T4 or T3 to inactive rT3 or T2, respectively. Type III deiodinase is found in cerebral cortex and skin, but also in several tisues of the fetus. It may be involved in metabolizing active thyroid hormone in the fetus to protect the fetal brain and other tissues from exposure to high levels of thyroid hormones.

As indicated above, the mammary gland of the rat has Type I deiodinase activity. However, there seems to be considerable species diversity in which type of deiodinase is present in the mammary gland. For example, the mammary deiodinase activity is Type II is the only activity present in the cow and mouse mammary glands, while both Type I and II are found in the sow's mammary gland. Deiodination of thyroid hormones by peripheral tissues, including the mammary gland, plays a primary role in regulating thyroid homeostasis, and therefore is indicative of the metabolic state of the animal and the particular tissue. With locally high activity of deiodiinase in the mammary gland results in local production of T3 which in turn stimulates metabolism in the gland.

So, in early lactation in the cow the excessive local conversion of T4 to T3 in the mammary gland may be reducing blood levels of T4. In addition, administration of T3 to the cow bypasses the T4-T3 conversion at the mammary level and provides greater T3 to the gland resulting in enhanced milk yield.

For more on deiodinases in general and in mammary tissue, see the reference list.

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