Endocrine Physiology Fall 2024 Lecture 3 PDF

3 physiology Barca Al-Qasrawi  Endocrine Physiology Fall 2024 Lecture 3 Hormonal regulation of lactation Functions of Prolactin Role of Oxytocin in lactations Zuheir A Hasan...

3 physiology Barca Al-Qasrawi  Endocrine Physiology Fall 2024 Lecture 3 Hormonal regulation of lactation Functions of Prolactin Role of Oxytocin in lactations Zuheir A Hasan Professor of Physiology College of Medicine HU 12/28/2024 1  Lecture Objectives Describe the physiological anatomy of the mammary gland Describe the development of breast during puberty , pregnancy and identify the role of different hormones in breast development Describe the chemical structure of prolactin , its duration of action and identify the pituitary cells which synthesize prolactin Describe the function of prolactin and its effects on mammary gland Describe the hypothalamic regulation of prolactin secretion and list factors which increases or decreases prolactin secretion Understand the regulation of prolactin secretion during pregnancy and during lactation Describe the neuroendocrine regulation of milk secretion and milk ejection. Describe the effects of oxytocin on mammary glands and its role in milk let down Describe the mechanism of and prolactin (Review) 12/28/2024 2  Physiological Anatomy of The Mammary. Gland A. The breast and its secretory lobules, alveoli, and lactiferous ducts (milk ducts) that constitute its mammary gland. B The enlargements show a lobule C milk- secreting cells of an alveolus 12/28/2024 3  Breast Development : Hormonal Regulation Development in breast at puberty is mainly due high levels of estrogens Estrogens of the monthly female sexual cycle; estrogens stimulate growth of the breasts’ mammary glands plus the deposition of fat to give the breasts mass More growth occurs during the high-estrogen state of pregnancy , full development of glandular tissue and the glands are ready for milk production High levels of estrogen during pregnancy cause further development of the duct system Final development of the breasts into milk-secreting organs also requires progesterone, specially during pregnancy. Growth hormone, prolactin, the adrenal glucocorticoids, and insulin also contribute to the development of the duct system Growth hormone, cortisol, parathyroid hormone, and insulin. These hormones are necessary to provide the amino acids, fatty acids glucose, and calcium required for the formation of milk. 12/28/2024 4  Physiological Actions of Prolactin Stimulates development of breast including growth and development of the mammary gland tissue and ductal proliferation. Stimulates milk production in the breast by Stimulating glucose and amino acid uptake by mammary epithelial cells. Increasing synthesis of the milk proteins β-casein and α- lactalbumin, the milk sugar lactose, and milk fats by the mammary epithelial cells. Inhibits spermatogenesis (by decreasing GnRH) when secreted in large amounts (Pituitary adenoma) Inhibits gonadotropin-releasing hormone (GnRH) during pregnancy leading to amenorrhea Modulates reproductive and parental behavior 12/28/2024 5 Here's a simplified breakdown: Estrogens: These hormones are crucial for breast development during puberty and the monthly menstrual cycle. They stimulate the growth of mammary glands and the deposition of fat, giving the breasts their mass. Pregnancy: During pregnancy, high levels of estrogen lead to further growth of the mammary glands and the duct system, preparing the breasts for milk production. Progesterone: This hormone, especially during pregnancy, is essential for the final development of the breasts into milk-secreting organs. Other Hormones: Growth Hormone, Prolactin, Adrenal Glucocorticoids, and Insulin: These contribute to the development of the duct system in the breasts. Growth Hormone, Cortisol, Parathyroid Hormone, and Insulin: These are necessary to provide the nutrients (amino acids, fatty acids, glucose, and calcium) required for milk formation. Breast Development: Prolactin helps in the growth and development of mammary gland tissue and the proliferation of ducts in the breasts. Milk Production: Prolactin stimulates milk production by: Encouraging mammary epithelial cells to take up glucose and amino acids. Increasing the synthesis of milk proteins (like β-casein and α-lactalbumin), milk sugar (lactose), and milk fats. Inhibition of Spermatogenesis: When prolactin is secreted in large amounts, such as in the case of a pituitary adenoma, it can decrease the production of GnRH (gonadotropin- releasing hormone), which in turn inhibits spermatogenesis (the production of sperm). Inhibition of GnRH During Pregnancy: Prolactin inhibits GnRH during pregnancy, which can lead to amenorrhea (the absence of menstrual periods). Reproductive and Parental Behavior: Prolactin also plays a role in modulating reproductive and parental behaviors.  The release of prolactin in response to suckling is neuroendocrine reflex Suckling Suckling reflexes + Mechanosensors in nipple + Hypothalamus Nerve pathway Increase prolactin-releasing factor Decrease prolactin-inhibitory hormone + + Posterior pituitary Anterior pituitary Increase oxytocin + Increase prolactin Contraction Myoepithelial cells + Increase milk ejection Increase milk secretion 12/28/2024 6 Sure, let's arrange and explain the information about the neuroendocrine reflex involved in prolactin release in response to suckling: Suckling: When a baby suckles at the nipple, it triggers a series of reflexes. Mechanosensors in Nipple: The suckling action stimulates mechanosensors (sensory receptors) in the nipple. Hypothalamus: These mechanosensors send signals through nerve pathways to the hypothalamus in the brain. Nerve Pathway: The hypothalamus responds by: Increasing the release of prolactin-releasing factor. Decreasing the release of prolactin-inhibitory hormone. Anterior Pituitary: These changes in hormone levels lead to an increase in prolactin secretion from the anterior pituitary gland. Posterior Pituitary: Simultaneously, the hypothalamus signals the posterior pituitary to release oxytocin. Oxytocin and Myoepithelial Cells: Oxytocin causes the contraction of myoepithelial cells around the mammary glands. Milk Ejection and Secretion: The contraction of these cells helps in the ejection of milk (milk let-down), while the increased prolactin levels stimulate further milk production. In summary, the suckling action initiates a neuroendocrine reflex that involves multiple steps and hormones, ultimately leading to increased milk production and ejection.  Prolactin levels during during pregnancy Although estrogen and progesterone are essential for physical development of the breasts during pregnancy, a specific effect of both these hormones is to inhibit the actual secretion of milk. Progesterone produce by the placenta during pregnancy interferes with prolactin binding to the receptors on the alveolar cells within the breast, thereby directly suppressing milk production during pregnancy Conversely, the hormone prolactin has the opposite effect and promotes milk secretion. Prolactin is secreted by the mother’s anterior pituitary gland, and its concentration in her blood rises steadily from the fifth week of pregnancy until birth of the baby, at which time it has risen to 10 to 20 times the normal nonpregnant level. Changes in prolactin levels after delivery Immediately after the baby is born, the sudden loss of both estrogen and progesterone secretion from the placenta allows the lactogenic effect of prolactin from the mother’s pituitary gland to assume its natural milk- promoting role, and during the next 1 to 7 days, the breasts begin to secrete large quantities of milk instead of colostrum. - Colostrum is the first form of milk produced by the mammary glands immediately following the delivery of a newborn. It is rich in antibodies, proteins, and nutrients, which are crucial for the newborn's immune system and overall health. Colostrum is typically yellowish in color and thicker than regular breast milk. It provides essential nutrients and helps protect the baby from infections during the first few days of life.  Changes in prolactin levels after delivery After the birth of the baby, the basal level of prolactin secretion returns to the nonpregnant level during the next few weeks. However, each time the mother nurses her baby, nervous signals from the nipples to the hypothalamus cause a 10- to 20- fold surge in prolactin secretion that lasts for about 1 hour milk production can continue for several years if the child continues to suckle, although the rate of milk formation normally decreases considerably after 7 to 9 months.  Effects of prolactin on ovulation High levels of prolactin during lactation and as lactation continues, suppresses ovulation because prolactin inhibits GnRH secretion by the hypothalamus and FSH and LH secretion by the anterior pituitary. Although not 100% effective, breastfeeding is method of contraception and family spacing in some regions of the world.  Changes in Secretion Rates of Estrogens, Progesterone, and Prolactin For 8 Weeks Before Parturition And 36 Weeks Thereafter. Changes in prolactin levels during pregnancy and during lactation High levels of estrogen , progesterone and prolactin DURING PREGNANACY High levels of prolactin is caused mainly by high levels of estrogen Progesterone produce by the placenta during pregnancy interferes with prolactin binding to the receptors on the alveolar cells within the breast, thereby directly suppressing milk production during pregnancy Note especially the decrease of prolactin secretion back to basal levels within a few weeks after parturition, but also the intermittent periods of marked prolactin secretion (for about 1 hour at a time) during and after periods of nursing. 12/28/2024 11  Physiologic effects of prolactin and its regulation b y dopamine Prolactin release is predominantly under negative feedback control by hypothalamic dopamine. Suckling of the nipples stimulates the release of prolactin by releasing the tonic inhibition of dopamine. Prolactin inhibits its own release by stimulating dopamine(feed back regulation) The release of prolactin in response to suckling is neuroendocrine reflex 12/28/2024 12 Let's break this down step by step: Negative Feedback Control by Dopamine: Prolactin release is mainly controlled by dopamine, a neurotransmitter produced by the hypothalamus. Dopamine inhibits prolactin secretion, meaning it keeps prolactin levels low under normal conditions. Suckling and Prolactin Release: When a baby suckles at the nipple, it triggers a neuroendocrine reflex. This reflex reduces the inhibitory effect of dopamine (releases the tonic inhibition), allowing prolactin levels to rise. Prolactin's Feedback Regulation: Prolactin can regulate its own levels through a feedback mechanism. High levels of prolactin stimulate the production of dopamine, which then inhibits further prolactin release. Neuroendocrine Reflex: The process of prolactin release in response to suckling involves both the nervous system (neuro) and the endocrine system (hormones), hence it's called a neuroendocrine reflex. In summary, prolactin release is normally inhibited by dopamine. Suckling reduces this inhibition, allowing prolactin to be released. Prolactin can then stimulate dopamine production to regulate its own levels. This entire process is a neuroendocrine reflex.  Regulation of Prolactin Secretion Factors that Increase Prolactin Factors that Decrease Prolactin Secretion Secretion Dopamine Estrogen (pregnancy) Bromocriptine (dopamine agonist) Breast-feeding Somatostatin Sleep Prolactin by negative feedback Stress Let's break down the regulation of prolactin secretion into factors TRH that incre. ase and decrease its levels: Factors that Increase Prolactin Secretion: Estrogen (Pregnancy): During pregnancy, high levels of estrogen stimulate prolactin production. Breast-feeding: Suckling by the baby triggers the release of prolactin to promote milk production. Sleep: Prolactin levels naturally rise during sleep. Stress: Physical or emotional stress can increase prolactin levels. Thyrotropin-Releasing Hormone (TRH): This hormone from the hypothalamus can stimulate prolactin release. Factors that Decrease Prolactin Secretion: Dopamine: This neurotransmitter inhibits prolactin secretion. Bromocriptine (Dopamine Agonist): This medication mimics dopamine's effects, reducing prolactin levels. Somatostatin: This hormone can inhibit prolactin release. Prolactin (Negative Feedback): High levels of prolactin stimulate the production of dopamine, which then inhibits further prolactin release. 12/28/2024 13  Disorders of prolactin secretion Hyposecretion ( Prolactin deficiency ) caused by : Infarction of pituitary ( Sheehan’s syndrome) Drugs (Dopamine agonist ) Hypersecretion : Caused by Hypothalamic damage (due to loss of the tonic “inhibitory” control by dopamine) sto a hormone-producing pituitary adenoma Prolactinomas are the most common tumors of pituitary gland Usually benign neoplasm. Patients with a prolactinoma present with elevated levels of prolactin (hyperprolactinemia) excessive secretion of milk (galactorrhea) reproductive dysfunction including loss of libido , amenorrhea In males, prolactinomas may cause infertility by producing hypogonadism due to inhibition of GnRH. can be treated with bromocriptine, which reduces prolactin secretion by acting as a dopamine agonist. 12/28/2024 14 Let's break down the disorders of prolactin secretion into simpler terms: Hyposecretion (Prolactin Deficiency): Sheehan’s Syndrome: This condition occurs when the pituitary gland is damaged due to severe blood loss during childbirth, leading to a deficiency in prolactin and other pituitary hormones. Drugs: Certain medications, like dopamine agonists, can reduce prolactin levels. Hypersecretion (Excess Prolactin): Hypothalamic Damage: Damage to the hypothalamus can reduce dopamine production, which normally inhibits prolactin. Without this inhibition, prolactin levels can rise. Pituitary Adenoma: A hormone-producing tumor in the pituitary gland can lead to excessive prolactin production. Prolactinomas: Most Common Pituitary Tumors: Prolactinomas are the most common type of pituitary gland tumors. They are usually benign (non-cancerous). Symptoms: Hyperprolactinemia: Elevated levels of prolactin in the blood. Galactorrhea: Excessive or inappropriate production of milk. Reproductive Dysfunction: This can include loss of libido (sexual desire) and amenorrhea (absence of menstrual periods). In Males: Prolactinomas can cause infertility by leading to hypogonadism (reduced function of the gonads, affecting hormone production and sperm development). In summary, disorders of prolactin secretion can involve either too little (hyposecretion) or too much (hypersecretion) prolactin. Hyposecretion can be caused by conditions like Sheehan’s syndrome or certain drugs, while hypersecretion is often due to hypothalamic damage or pituitary tumors like prolactinomas. These conditions can lead to various symptoms, including reproductive issues and inappropriate milk production.  Mechanism of prolactin on breast and mammary glands Prolactin is a polypeptide hormone that is synthesized in and secreted from specialized cells of the anterior pituitary gland, the lactotrophs. The effects of prolactin on the breast and mammary gland are mediated by Tyrosine Kinase Signaling receptors Hormone receptor biding that stimulates the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway Commonly known as the JAK/STAT signaling pathway This topic is explained in second biochemistry Lecture 12/28/2024 15