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Hormones and Mammary Growth. TGF- b Effect on Mammary Growth in Culture. Epidermal Growth Factor and Mammary Growth. Major Endocrine Organs. Ovary Corpus Luteum Follicle. Brain. Hypothalamus. Adrenal Cortex Medulla. Thyroid. Kidney. Pituitary Anterior Posterior.
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Major Endocrine Organs Ovary Corpus Luteum Follicle Brain Hypothalamus Adrenal Cortex Medulla Thyroid Kidney Pituitary Anterior Posterior Parathyroid Placenta Pancreas Islets of Langerhans
Hypothalamus Anterior Pituitary Adipose Lipolysis CRF Liver Gluconeogenesis Inhibit Insulin Action ACTH Glucocorticoids Muscle Protein Breakdown Adrenal Cortex Medulla Mammary Lactogenesis Lactation Kidney
Hypothalamus Anterior Pituitary Cold TRH Temperature Regulation TSH Increased Basal Metabolic Rate Thyroid Thyroxin
Hypothalamus Follicular Development Anterior Pituitary GnRH Uterus Growth Brain Sexual Behavior FSH Estrogen Follicles Growth Mammary Gland Duct Growth Increased Progesterone Receptor
Hypothalamus Ovulation Anterior Pituitary Uterus Maintains Pregnancy GnRH Corpus luteum formation Estrogen + Progesterone Brain Sexual Behavior Estrogen + Progesterone LH Estrogen Estrogen + Progesterone Follicle Ovuation Corpus luteum Mammary Gland Alveolar Growth together with estrogen
Hypothalamus Anterior Pituitary Adipose Lipolysis Inhibit insulin action Somatostatin Inhibits GH GHRH Liver Gluconeogenesis Inhibit Insulin Action Muscle Protein synthesis or Breakdown Inhibits insulin action Body Growth Mammary Increased Nutrient uptake Increased blood flow.
Hypothalamus Anterior Pituitary Dopamine Inhibits Prl CL of Most Rodents CL formation Progesterone production (LH still induces ovulation) TRF Mammary Lactogenesis, Lactation (some Species)
Pancreas Adipose Glucose uptake Fat synthesis Intestine Liver Glucose uptake Glycogen synthesis Inhibits gluconeogenesis Muscle Glucose uptake Glycogen synthesis Amino acid uptake Protein synthesis Islets of Langerhans Insulin Cells Glucagon Opposite of insulin in liver and muscle Mammary Little effect Increases glucose uptake Amino acid uptake Cells Produce Insulin
Brain ? Food Intake Mammary Growth Placental Lactogen Various Organs Nutrient Partitioning ? Uterus Caruncle Maternal Side of Placenta Cotyledon Fetal Placenta Produces Placental Lactogen
Estrous Cycle of Cow 12 10 8 6 4 2 0 0 0 3 6 9 12 15 18 21 Progesterone Estrogen Day of Cycle
Peripuberal Mammary Growth Weeks 3-6 in Mice 2.5 End Bud Area Duct Length 2.0 1.5 Area (mm Sq) or Length (mm) 1.0 0.5 0.0 Control OvX Ovx + E Ovary on Growth
Estrogen ActionsEndocrine Epithelium Estrogen Cell Division
Estrogen ActionsParacrine Estrogen Stroma Growth Factors Cell Division
Estrogen ActionsAutocrine Estrogen Growth Factors Cell Division
Hormone Changes During Pregnancy in Cows 30 20 Prolactin Progesterone, Prolactin, Placentl Lactogen (ng/ml) Progesterone 10 Estrogen Estrogen (pg/ml) Placental Lactogen 0 0 50 100 150 200 250 Days Pregnant
E+P on Mammary Growth Postpuberal Mice 1.2 1.0 0.8 Epithelial Volume (mm Cu) 0.6 0.4 0.2 0.0 Control E P E+P Synergy Additive Response
Estrogen and Progesterone Actions Epithelium Estrogen increases progesterone receptor Increases growth Progesterone Increases growth Alveolar formation Cell Division Autocrine and paracrine actions are similar to estrogen alone.
Placental Lactogen on Mammary Growth 10 - E+P 8 + E+P 6 % Labeled Epithelial Cells 4 2 0 0 5 25 Bovine Placental Lactogen (µg/day)
Prolactin and Growth Hormone • Variable among species • Mice • Pituitary required for growth • Which hormone depends on strain • Cows • Little effect of prolactin on growth • Maybe some of growth hormone • May be indirect • At least some effects indirect • Somatomedin (IGF-I) from liver • Nutrient partitioning