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Galactopoiesis Part II : Roles of Hormones Part I: Overview Part III: Milk removal & Autocrine Illinois Module : Lactation Dynamic changes in mammary gland of lactating goat Knight, C . and M. Peaker (1984, Quarterly J. Exper. Physiol. 69:331). Weeks of Lactation Milk Yield Cell Numbers Yield per Cell 1 Phase of the Lactation Curve Ascending Increasing Increasing 2 Ascending Increasing Increasing 3 Ascending Increasing Increasing Increasing 4 Ascending Increasing Static Increasing 5 Ascending Increasing Static Increasing 6 Ascending Static 7 Peak Static 8 Peak Static Declining 8 - 11 Peak Declining Declining 11 - 23 Declining Declining Declining 23 - 36 Late lactation, pregnant Declining Static Declining Dynamic changes in mammary cell regulated by galactopoietic hormones and local mammary factors Role of Prolactin Role of Prolactin primary component of the galactopoietic complex of hormones Species variability in PRL role lactating rabbit, PRL is galactopoietic PRL + glucocorticoid restore lactation in hypox. rats GH + PRL + glucocorticoid improve lactation PRL + GH + glucocorticoid + T4 restore lactation in hypox. goat PRL maintain lactation in nonruminants suppression PRL by bromocriptine or L-DOPA reduce lactation performance antisera to PRL receptors inhibits PRL- induced casein synthesis and milk yield decreased PRL in ruminants Galactopoietic of PRL is less clear in ruminants – Suppression of PRL in cows and goats by bromocriptine has minimal effects on milk yield – In lactating ewe, bromocriptine markedly reduces milk yield But, PRL is necessary for full lactogenesis in cattle Suckling or milking induces PRL surge •PRL surge (green line) 3-fold increase over non-stimulated (blue hatched line) • PRL surge occurs over half an hour after milking or nursing • oxytocin surge only lasts about 5 to 10 minutes (red box) • milking-induced PRL surge small compared with peripartum (Tucker, surge of PRL associated with 1994) lactogenesis Suckling or milking induces PRL surge milking-induced PRL surge, a direct link between nursing or milk removal and galactopoietic hormones galactopoietic response to nursing intensity (litter size) in pigs or rodents may involve amount of PRL released at nursing effect of suckling on PRL declines with advancing lactation, even if nursing stimulus is kept equivalent throughout lactation Suckling or milking- induced PRL surge may work by … decreasing increase PIF from hypothalamus pituitary response to PRL-RF milk yield & PRL in dairy cattle no correlation between milk yield and PRL levels 2-4 hr before milking or 1 hr after milking, but 5 min. post-milking Many stimuli alter PRL levels, especially TEMPERATURE and LIGHT temperature increases, PRL increase day-length increases, PRL increase – response lags a few days after day-length change PRL also respond to stress – Great care must be taken when collecting blood samples , not to stress animal Growth Hormone - bST Growth Hormone - bST Nursing increased GH in rat and goat, but not in lactating cow or lactating woman GH decreases with advancing lactation In rats - GH has little effect on established lactation In ruminants - GH is clearly galactopoietic Bovine Somatotropin (bST) bST increase MY, 10% in early to mid-lactation, and up to 40% during late lactation bST-treated cows partition nutrient to support increased milk output bST seem not to affect cow's health other than problems normally with high milk production Mastitis incidence is not affected by long term administration of bST bST increases synthesis of lactose, fat and protein in mammary gland bST slightly alters milk composition Photoperiod on Growth and Milk Production in Cattle Dahl et al. (2000 Light on growth in heifers: 16 hr of light daily increased rate of body growth 10-15% w/o proportional increase in feed intake due to protein gain, not body fat increase PRL, but not GH Light on in heifers: 16 hr of light daily stimulate mammary growth in prepubertal and postpubertal heifers increased milk yields by about 10% during fall and winter intake increased sufficiently to account for increased milk yield Placental Lactogen Placental Lactogen: PL Cattle often lactating and pregnant at the same time, So, Placental hormone may affect mammary function bPL given during lactation increase MY mechanism of PL as galactopoietic effect differ from BST [See Byatt et al., 1992, J. Dairy Sci. 75:1216.] goat is not lactating and pregnant at the same time (except in very late lactation) So, very high levels of caprine-PL found in pregnant goat's blood Thus, PL have a dramatic effect on mammary development in goat PL found in at least 9 species, but presence of PL in cattle is doubtful Where PL found, it may mimics PRL or GH actions Adrenal and Thyroid Hormones Adrenal corticoids essential high for maintenance of lactation doses inhibit lactation rats, lower doses stimulates MY in early lactation and prevents decline MY in later lactation ruminants, high doses inhibitory effects, but lower doses ambiguous adrenalectomized rat impaired milk secretion and casein mRNA decreased by 85-92%, Cortisol reverse Adrenalectomy-ovariectomy stops lactation completely In rat, adrenal secretions are limiting – ACTH declines in extended lactation – Corticoid binding globulin declines during early lactation, increases during later lactation – So, effective corticoids decline In cattle, no change in CBG during lactation – so Corticoids are not limiting to milk yield in cows, but still essential Thyroid Hormones *** are essential for maximal secretion of milk Thyroidectomy cattle decreased MY Injection for 7 weeks at 25% above normal thyroid secretion increase MY by 27% continued at 150% for 7 more weeks had little or no effect Feeding thyroprotein (iodinated casein) to cows – increases MY by 10 % in early lactation and by 15-20% in late lactation – effect lasts 2-4 mos. and subsequent yields are below normal no net benefit in feeding thyroprotein over entire lactation Ovarian Steroid Hormones Ovarian Steroid Hormones Ovariectomy has no effect on postpartum mammary growth or lactation, suggesting that ovarian steriods are not necessary for maintenance of lactation On the other hand, increased estrogen may affect milk production concurrent pregnancy influence persistency of milk yield in declining phase of lactation, dairy cattle Inhibitory effects of pregnancy on lactating cows apparent about mid pregnancy mechanism of this effect is not fully understood P4 seems no effect on MY in lactating cow because – P4 has higher affinity for milk fat than glucocorticoid – No P4 receptors in the mammary gland during lactation However, timing of inhibition of milk yield in cattle coincides approximately with the period of increasing placentally-derived plasma estrogen pharmacological doses of E2 decrease MY E2 in late lactation enhance mammary gland undergoes involution at drying off A role for E2 in mammary gland involution in dairy cattle has been indicated Further reading HorLactation.doc