17.

6 Hormonal Control of Lactation Appreciable mammary secretions are produced only after the formation of the lobule-alveolar system. Thus, in the pregnant heifer secretion does not commence until the second half of gestation. Many of the enzymes needed for milk synthesis are present within the cells of the udder well in advance of calving.14 At parturition hormones cause a tremendous increase in the amount of secretion. The secretions formed prepartum are colostral in nature and not true milk. The subsequent secretion of large amounts of milk is dependent upon a preexisting and extensive development of the udder. Initiation of Lactation During pregnancy progesterone apparently blocks the secretion of a-lactalbumin, a milk protein that is also an enzyme needed for the synthesis of lactose, the sugar found in milk.15 This block is sufficient to inhibit milk synthesis during most of the gestation period of the heifer. Also, high titers of progesterone probably inhibit the initiation of lactation in multiparous cows during the dry period. The progesterone block is ineffective during concurrent lactation and pregnancy; otherwise, lactation would be inhibited as soon as the lactating cow conceived. Why progesterone inhibits lactation in one instance and not in another is not known yet. Shortly before parturition, progesterone titers fall (which removes the block) andjsstrogen, ACTH (which stimulates adrenal corticoid secretion), and prolactin levels increase. The administration of adrenal corticoids or estrogen will initiate lactation in dairy cows. Although not tested in cows, prolactin will initiate lactation in some but not all species. The use of these hormones to induce lactation in cows is discussed in Section 17.7. Neural stimuli are not normally required to initiate lactation. However, the milking stimulus (which sends neural impulses to the hypothalamus and pituitary) will initiate lactation in heifers during late gestation. This prepartum milking probably causes the release of prolactin and ACTH (and adrenal corticoids) which actually initiate lactation. As discussed in Chapter 19, this practice is not recommended. Maintenance of Lactation After parturition there is a rapid increase in milk yield in cows, which reaches a maximum in 2 to 6 weeks. Then it gradually declines. The degree of maintenance of milk production is called persistency. Thus, after the maximum is reached, the decline in milk production each month can be calculated as a percentage of the previous month's production, and this percentage is a measure of persistency. Dairy cows normally lactate 10 to 12 months, but there is a report of one cow that lactated continuously for 5 consecutive years. The following terminology will be used to describe lactation: Milk secretion involves both the intracellular synthesis of milk and its subsequent passage from the cytoplasm into the alveolar lumen. Milk removal involves both the passive withdrawal of milk from the cisterns and major ducts and the active ejection of milk caused by contraction of the myoepithelial cells around the alveolus in response to oxytpcin. Lactation includes both milk secretion and milk removal. The term galactopoietic pertains to the ability of certain factors to enhance an established lactation. Milking Stimulus. To support intense lactation, the number of secretory cells, their metabolic activity, and an efficient milk ejection reflex must be maintained. The milking stimulus is important for the maintenance of mammary structure and lactation. For example, if milking is stopped, milk synthesis stops, and the secretory cells of the udder are rapidly lost. In cows, milking causes the release of prolactin from the anterior pituitary into the blood (Table 17.1). However, the prolactin response to milking probably lasts less than 30 minutes, and its significance in relation to the basal levels that are continuously present in the blood is unknown. In addition to prolactin, milking causes a discharge of ACTH (and adrenal glucocorticoids) from the anterior pituitary and oxytocin from the posterior

pituitary, all of which help to maintain lactation. However, milking stimuli without accompanying milk removal will not maintain lactation. The relative importance of milk removal and stimulation of hormone release from the pituitary in the maintenance of lactation is still undetermined. In any event, to promote maximal synthesis, cows should be milked out completely at least twice daily (Chapter 19). Hormonal Factors. The experimental approach used to elucidate the hormonal factors necessary to maintain lactation has usually involved endocrine gland removal followed by hormonal replacement therapy. Hypophysectomy, adrenalectomy, or thyroidectomy cause a rapid decline in milk production. The following experiments serve to illustrate the hormones needed to develop the gland and to initiate and maintain lactation.16 Adult rats were hypophysectomized, adrenalectomized, and ovariectomized. Mammary growth was induced with a combination of estrogen, progesterone, prolactin, growth hormone, and adrenal corticoids. Lactation was then initiated with prolactin and adrenal corticoids. Maintenance of lactation required prolactin, growth hormone, and adrenal corticoids. 17.7 Artificial Induction of Lactation Of all the cows culled in dairy herds about 15 to 20 are culled for infertility. Naturally as soon as milk production declines to unprofitable levels, these barren animals are culled from the herd. Much research has been performed in attempts to reinitiate the secretion of large quantities of milk in these animals. The problem is twofold: (1) udder growth must be induced and (2) these cells must be stimulated to produce milk. To develop the udder, most investigators have injected, implanted under the skin, or fed various combinations of estrogen and progesterone. Treatment with these hormones has produced variable amounts of udder growth, and subsequent milk production has ranged from 0 to 80 Ib per day. However, the majority of the treated cows produce subnormal quantities of milk. Up to the present time, injection of ovarian steroids has not duplicated the mammary growth response of pregnancy. Provided sufficient numbers of alveolar cells are present, lactation can be induced in dairy cattle within a few days with either adrenal glucocorticoids or high levels of-estrogen (Figure 17.13). However, use of these hormones should be restricted to nonpregnant cows because either hormone will cause abortion. In fact, estrogen injection is the common method used to cause abortion of unwanted fetuses. Subcutaneous injection of a total daily dose of 0.05 mg/kg body weight of estradiol-17/5 and 0.125 mg/kg body weight of progesterone dissolved in 100 ethanol will initiate lactation in about 60 to 70 of barren heifers and cows.18 Daily dose is divided in half and injected at 12-hour intervals for 7 days. The percent success rate (daily yield greater than 9 kg) has recently been increased to 100 if 5 mg of the tranquilizing drug, reserpine, is administered on days 8, 10, 12, and 14.19 Reserpine causes an increase in serum prolactin in these cows. The steroid and prolactin profiles in serum mimic the normal changes in these hormones during the periparturient period. Lactation usually commences between days 14 and 21 after initial injections of estradiol-17/5 and progesterone. Cattle should be restricted in their movement because of intense symptoms of estrus after day 7. The quantity of milk produced in treated cows is usually about 70 of their best previous lactation. At the present time these treatments are experimental only, and they have not been cleared for commercial use by the Food and Drug Administration of the U.S. government. Furthermore, until more repeatable responses in milk production are obtained, there is little justification to attempt artificial induction of lactation. 17.8 Hormonal Stimulation of Lactation

At the present time only one hormone, thyroprotein, has been cleared by the Federal Food and Drug Administration for commercial use in dairy cows to stimulate lactation. However, there are some other hormones that will increase milk production, although their use is restricted currently to experimental purposes. Thyroprotein Thyroprotein is a synthetic hormone made by the iodination of casein, the major milk protein. It mimics the biological action of thyroxine and triiodothyronine. This hormone is inexpensive and orally active. Thyroprotein fed to dairy cows at the peak of lactation will stimulate milk production about 10, whereas if fed during the declining phase of lactation, average milk production is boosted 15 to 20.20 However, the response is extremely variable among individual cows. Usually a greater increase in milk production occurs in higher-producing cows and older cows. The maximal increase usually occurs during the first 60 days of thyroprotein feeding. However, the beneficial effects disappear within 2 to 4 months. In fact, subsequent milk production is often below that normally expected. The net result on milk production in controlled experiments over an entire lactation suggests that thyroprotein-fed cows do not produce significantly more milk than control cows. Thyroprotein has no serious effects on health, longevity, or reproductive function. Usually there is some weight loss, and increased heart and respiration rates will be noticed, but these effects are largely dependent upon the dose given. As recommended in Chapter 11, thyroprotein should not be fed unless energy intake is increased substantially. Thus, if feed intake must be increased and the overall benefit to milk production from feeding thyroprotein is negligible, this practice would not generally be economical. Still, thyroprotein will increase milk production at least temporarily. The current practice is to feed thyroprotein when milk production declines below 50 to 60 Ib of milk daily. Thyroprotein should be given only to cows gaining in body weight, and it should be discontinued if the cow does not respond within 2 weeks.21 A marked decline in milk production to below normal levels occurs whenever thyroprotein is abruptly removed from the ration. A better practice is to remove the hormone from the ration gradually. Even with this precaution, reduced milk yields may occur. Thyroprotein should be withdrawn about 2 weeks before the cow is dried off. Growth Hormone Experiments in the 1930s showed that crude extracts of the anterior pituitary were galactopoietic in ruminants. The growth hormone content of these extracts probably caused most of this stimulation. Because growth hormone is not commercially available, only short-term lactation trials have been conducted, but about 18 increases in milk production can occur within a few days after injecting growth hormone only 3 times per week into dairy cows.22 Furthermore, feed intake per kg milk was reduced 29. Adrenal Glucocorticoids Many published reports suggest that injection of ACTH or adrenal steroids depresses lactation in cows. However, experiments have shown that lactation in rats can be maintained well beyond the usual period with adrenal corticoid supplementation.23 Although there are reports to the contrary, a recent study shows that feeding a very low dose of asynthetic glucocorticoid may stimulate milk yield 14 to 18.24 Ovarian Steroids The feeding of progestins used in estrous synchronization for 18 days has no significant effect on milk production in dairy cows. Within a very low and narrow dosage range, estrogen and the synthetic

estrogen, stilbestrol, are galactopoietic in dairy cows. More commonly, however, estrogens in the dosages usually employed in veterinary medicine inhibit lactation in cows. This therapy is often employed in post-partum women not wanting to breast-feed their infants. A combination of estrogen and progesterone is even more inhibitory than estrogen alone. Thus, we are left with the paradox whereby estrogen can initiate lactation and then subsequently reduce milk yields. Photoperiod In a preliminary study in Michigan, exposure of growing Holstein heifers to 16 hours of fluorescent light and 8 hours of darkness daily between November and March increased serum prolactin fourfold and increased rate of body weight gain approximately 12 in comparison with heifers receiving day lengths characteristic of Michigan's fall and winter.25 The 16-hour light period stimulated milk production more than 10 during fall and winter in lactating dairy cows.

(Bath)