Hormonal Control of Pregnancy and Lactation Early Embryonic

Hormonal Control of Pregnancy and Lactation

Early Embryonic Development • After fertilization, the embryo spends the first four days in the oviduct (fallopian tube) • The developing embryo is then transferred to the uterus, and implants in the uterine endometrium • By day 6, the trophoblast cells of the embryo begin to produce h. CG • In a normally developing embryo, h. CG levels (in maternal circulation) will double every 3 days, reaching peak at about 2 months of pregnancy Dr. M. Alzaharna (2014) 2

Progesterone Levels • To maintain the uterine endometrium and inhibit contraction of myometrium, plasma progesterone levels must be maintained during pregnancy • Early in pregnancy, this is accomplished by the action of human chorionic gonadotropin (h. CG) on the corpus luteum (first 8 weeks of pregnancy) • Later in pregnancy, progesterone is produced by the placenta Dr. M. Alzaharna (2014) 3

Actions of Human Chorionnic Gonadotropin (h. CG) • h. CG binds to the LH receptor in the corpus luteum, maintaining luteal steroidogenesis during the first 8 weeks of pregnancy • In addition, h. CG may act to stimulate testosterone production from the developing testes in male embryos Dr. M. Alzaharna (2014) 4

Steroid Production by The Placenta • Later in pregnancy, the placenta becomes the major steroidogenic organ of pregnancy • However, the placenta requires maternal LDL as a source of cholesterol for progesterone production • The placenta is dependent upon the maternal and fetal adrenal as a source of androgens for aromatization to produce estrogen • Estrogens may be important in increasing uterine blood flow to the fetus, and in the maturation of fetal organ systems Dr. M. Alzaharna (2014) 5

Parturition: The Process of Childbirth • The mechanisms signaling the onset of labor are not clearly understood, although several theories exist – Potential role of progesterone • decreasing progesterone prior to labor would allow uterine contractions to occur • however, there is no decline in progesterone before labor in humans • some studies suggest there is a decline in uterine progesterone receptors, resulting in decreased progesterone action, leading to labor Dr. M. Alzaharna (2014) 6

Positive feedback cycles that contribute to initiation of parturition CRH: corticotropin releasing hormone. Green arrows indicate stimulation; red arrows indicate inhibition 7

Potential Role of Oxytocin in Parturition • Oxytocin causes uterine contraction • However, oxytocin levels do not increase until after labor starts, according to more recent studies • Oxytocin may play a role in uterine contraction following labor, resulting in decreased blood loss Dr. M. Alzaharna (2014) 8

Potential Role of Relaxin in Parturition • Another marker of corpus luteum function is the polypeptide hormone relaxin • Relaxin becomes detectable at about the same time as h. CG begins to rise, and certain concentrations are maintained for the remainder of the pregnancy until labor • Relaxin also decreases uterine contractility during pregnancy • Relaxin acts on the cervix, causing dilatation and softening • Relaxin does act to soften connective tissues, such as the ligaments connecting the pelvic bones, to allow increase in size of the birth canal Dr. M. Alzaharna (2014) 9

Potential Role of Prostaglandins in Parturition • Prostaglandins cause dilation and softening of the cervix • Prostaglandins also cause uterine contractions • The levels of prostaglandins increase in fetal membranes before the onset of labor Dr. M. Alzaharna (2014) 10

Lactation • Lactation is the delivery of milk from the mammary gland • There are four main stages of lactation, controlled by different hormones: 1. 2. 3. 4. Milk synthesis in alveolar cells Lactogenesis: Secretion of milk from alveolar cells to alveolar lumen Galactopoiesis: Maintenance of milk production and release into alveolar lumen Milk ejection: movement of milk from alveoli into the duct system and out of the breast Dr. M. Alzaharna (2014) 11

Lactation 1 - Milk Synthesis – Production of breast milk is stimulated by increased levels of prolactin (pituitary) and human placental lactogen (HPL) (from the placenta) during pregnancy – Milk release from alveolar cells is inhibited by the high levels of progesterone and estrogen during pregnancy – Estrogen and progesterone also act with prolactin to increase alveolar duct growth during pregnancy Dr. M. Alzaharna (2014) 12

Lactation 2. Lactogenesis – Stimulated by prolactin, and occurs after parturition when estradiol and progesterone levels are decreased 3. Galactopoiesis – The maintenance of established milk production, caused by prolactin 4. Milk Ejection – Movement of milk from alveolar ducts into the main duct system and out of the breast is induced by oxytocin – Oxytocin causes contraction of myoepithelial cells in the breast, causing milk release Dr. M. Alzaharna (2014) 13

Regulation of Oxytocin and Prolactin During Lactation • There is a positive feedback effect of breastfeeding on the production of oxytocin and prolactin • Oxytocin levels increase due to suckling of the breast by the infant • In addition, sight, sound, or thought of the infant can also increase oxytocin levels, causing milk ejection • Prolactin release is also increased by suckling of the breast by the infant (but not by audiovisual stimuli) Dr. M. Alzaharna (2014) 14