RCSI Hypothalamus-Pituitary Target Organ Axes Feedback Control 1 PDF

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Hypothalamus - Pituitary Target Organ Axes: Feedback Control 1 Class Year 2 Course Endocrine and Breast Module Presented by Dr Brona Murphy/Dr Ebrahim Rajab Date January 2025  LEARNIN...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Hypothalamus - Pituitary Target Organ Axes: Feedback Control 1 Class Year 2 Course Endocrine and Breast Module Presented by Dr Brona Murphy/Dr Ebrahim Rajab Date January 2025  LEARNING OUTCOMES Outline the role of the hypothalamus & pituitary gland within the endocrine system Describe the basic function of the anterior pituitary hormones in the body Describe the basic function of the posterior pituitary hormones in the body Differentiate between the vascular & neural connections of the hypothalamus to the pituitary gland Outline how the hypothalamic hypophysiotropic hormones regulate anterior pituitary hormone secretion Describe the role of feedback by target gland hormones in the regulation of anterior pituitary hormone secretion Endocrine System and hormones A major regulatory system that co-ordinates life-sustaining responses. Made up of several hormone-producing “endocrine glands” (e.g. pituitary and thyroid glands). – They are ductless (in comparison to exocrine glands) and release hormones directly into the bloodstream. Found in various locations within body In addition, there are various isolated endocrine cells found in other tissues of the body, (e.g. G cells of stomach, which secrete gastrin). Referred to as the ‘diffuse endocrine system’.  Endocrine System and hormones The hormones act on their target cells to regulate plasma concentration of nutrient molecules, water, salt & other electrolytes Hormones also play a role in regulating – metabolism – controlling growth and development – reproduction – stress adaptation  Hypothalamus Considered the coordinating center of the endocrine system Less than 1% of brain mass; about size of a peanut Below thalamus & above pituitary on either side of 3rd ventricle Connected with many areas of the brain & spinal cord - particularly limbic system & autonomic brainstem areas Fitzgerald's Clinical Neuroanatomy and Neuroscience, 34, 368-375  Hypothalamus Acts as an interface between internal & external environment. External (sensory) Sensory pathways conveying info on external environments (e.g. light, temperature, nociception) Internal (sensory) Receptors of body temperature, osmolarity, pressure, volume, glucose concentration, hormone concentration External responses behaviors required for survival and reproduction: Intense feeding, drinking, aggressive, and sexual behaviors − Appetite, emotional, instinctual − Connections with CNS Internal homeostatic responses Produced through ANS & endocrine system Endocrine link is through the hypothalamic-pituitary axis  PITUITARY GLAND/HYPOPHYSIS Small gland http://bp3.blogger.com/_biVHanHPi_4/RoNs7NBycwI/AAAAAAAAAVM/c 1 cm in diameter & 0.5-1 g in weight Lies in the sella turcica (Turkish saddle) Bony cavity in base of brain Physiologically divided into 2 distinct portions Anterior pituitary/adenohypophysis Posterior pituitary/neurohypophysis Embryologically these 2 portions originate from different sources Pituitary Gland/Hypophysis – embryology Anterior pituitary Arises from an upward and outward pouching from the epithelium of the pharynx (Rathke’s pouch) Explains the epitheloid nature of its cells Posterior pituitary Arises from a neural tissue outgrowth from the hypothalamus Large number of glial-type cell Hypothalamus & Pituitary HYPOTHALAMUS & PITUITARY GLAND This unit forms a complex & dominant component of entire endocrine system Essential for survival Coordinating Center: The hypothalamus is the central hub of the endocrine system Consolidates Signals: From brain's upper areas (cortical inputs) From autonomic functions (automatic body functions) From environmental cues (like light and temperature) From peripheral endocrine systems (feedback from other hormones). Delivers Signals: Sends precise signals to the pituitary gland. Pituitary Gland Activation: The pituitary then releases hormones affecting various endocrine systems throughout the body  Hypothalamus and Pituitary gland Release of hormones from both the posterior and anterior pituitary is controlled by either nervous or hormonal signals from the hypothalamus Anterior pituitary connects by a unique vascular link Posterior pituitary connects to the hypothalamus by a neural pathway ANTERIOR PITUITARY CELL TYPES & HORMONES The anterior pituitary is composed of several different cell types that synthesize and secrete hormones. Cell types Hormones Somatotrope Growth Hormone (GH) (30-40% of anterior pituitary cells) Thyrotrope Thyrotropin/Thyroid Stimulating Hormone (TSH) Lactotrope Prolactin (PRL) Gonadotrope Luteinizing Hormone (LH) & Follicle Stimulating Hormone (FSH) Corticotrope Adrenocorticotropin (ACTH) (20% of anterior pituitary cells) Terminology : “trophic”, “troph”, “trope” Tropic hormones, also known as tropic factors or tropins, regulate the secretion and activity of other hormones within the endocrine system. These hormones are typically produced and released by specific glands in the body, and their primary function is to stimulate or inhibit the secretion of hormones from target glands. PRL only one that does not stimulate secretion of another hormone  FUNCTIONS OF ANTERIOR PITUITARY HORMONES GH: Stimulates secretion of insulin-like growth factor 1 (IGF-1), from liver and other organs, which is responsible for GH’s anabolic effects. Stimulates lipid and CHO metabolism TSH: Stimulates synthesis and secretion of thyroid hormones and regulates thyroid cell proliferation and survival ACTH: Simulates synthesis and secretion of adrenal cortex steroids (e.g.- cortisol) and proliferation and survival of adrenal cortex cells. Prolactin: Stimulates milk production LH: Females: induces ovulation and progesterone synthesis Males: stimulates testes to produce testosterone FSH: Females: Stimulates estrogen synthesis, promotes follicular growth Males: promotes spermatogenesis HYPOTHALAMUS & ANTERIOR PITUITARY  Regulation of Anterior Pituitary Hormone Secretion Two important factors that regulate anterior pituitary hormone secretion 1. Hypothalamic hypophysiotropic hormones 2. Feedback by target gland hormones and physiological effects/responses Hypothalamic hypophysiotropic hormones Hypothalamic releasing & hypothalamic inhibitory hormones (factors) Synthesized, packaged into vesicles and transported down the axons of Hypothalamic hypophysiotropic neurons within hypothalamus. Sorted and released from nerve terminals Transported to anterior pituitary, in high concentrations, by the Hypothalamic-hypophyseal portal system Bind to receptors on glandular cells in anterior pituitary to modify secretion of hormones. Hypothalamic hypophysiotropic neurons often secrete in a pulsatile manner and are entrained to daily and seasonal rhythms through CNS inputs. These neurons also receive input from higher and lower levels of the brain (e.g. stress, infection, puberty) HYPOTHALAMIC HYPOPHYSEAL PORTAL SYSTEM  Hypothalamic Hypophysiotropic Hormones Small peptide hormones Primary action apparent from its name e.g. Thyrotropin Releasing Hormone (TRH) stimulates release of Thyroid Stimulating Hormone (TSH)(also known as Thyrotropin) Many have more than one effect – Prolactin Inhibitory Hormone (PIH) is identical to dopamine A single anterior pituitary hormone may be regulated by two or more hypothalamic hypophysiotropic hormones – Growth hormone regulated by GHRH & GHIH – Rate of GH secretion depends on relative concentrations of these hypothalamic hypophysiotropic hormones  Hypothalamic Hypophysiotropic Hormones Hypothalamic hormones When the link between the hypothalamus and the anterior pituitary is disrupted, such as from damage to the pituitary stalk due to surgery, the production of all anterior pituitary hormones typically decreases, with the exception of prolactin, whose levels rise. This rise in prolactin occurs because the persistent inhibitory influence, known as prolactin-inhibiting factor (PIF), is eliminated. Hypothalamic Hypophysiotropic Hormones TRH, CRH, GHRH, somatostatin, and PIF/PIH synthesized in arcuate and paraventricular nuclei (PVN) GnHRH synthesized in pre-optic nucleus Fitzgerald's Clinical Neuroanatomy and Neuroscience, 34, 368-375  FEEDBACK BY TARGET GLAND HORMONES AND PHYSIOLOGICAL EFFECTS/RESPONSES Physiological response-driven negative feedback Hypothalamic neuroendocrine neurons Endocrine Gland Negative Feedback Circulating Releasing Hormones component (e.g.- blood glucose) Pituitary Gland Hormone Tropic Hormone Peripheral endocrine Physiological gland Effects Target Organ Physiological Target Hormone Effects Organs  Feedback Control Mechanisms Hormone secretion is controlled by the following feedback mechanisms: 1. Negative feedback : Ultrashort feedback loop: Hypothalamic hormones inhibit their own secretion via autocrine effects. Short feedback loop: Pituitary hormones inhibit the release of hypothalamic hormones. Long feedback loop: Hormones from peripheral endocrine glands inhibit the release of hypothalamic and pituitary hormones. 2. Positive feedback Hormone secretion enhances its own production. (e.g., prior to ovulation in the female reproductive cycle)  HYPOTHALAMUS & POSTERIOR PITUITARY Form a neuroendocrine system consisting of neurosecretory neurons whose cell bodies lie in two well defined clusters in the hypothalamus – supraoptic & paraventricular nuclei  (Arginine) Vasopressin (AVP)/Antidiuretic Vasopressin & Oxytoxin hormone (ADH)- primarily formed in the supraoptic nuclei. Oxytocin– Primarily formed in the paraventricular nuclei. Each of these nuclei can synthesize 1/6th as much of the second hormone as of its primary hormone. Synthesized as prohormones Transported along axon to the nerve endings in the posterior pituitary gland. Requires several days. In combination with “carrier proteins”- Neurophysins. Upon nerve impulse stimulation, hormone is released (from the axon endings) by exocytosis. Both neurophysin & hormone are secreted. Separate almost immediately. Hormone absorbed by adjacent Source: Endocrine and Reproductive Physiology. capillaries White, Bruce A., PhD; Harrison, John R., PhD; Mehlmann, Lisa M., PhD. 2019  SUMMARY: HYPOTHALAMUS-PITUITARY-TARGET ORGAN AXIS Hypothalamus: Central regulator, sends releasing hormones. Pituitary Gland: o Anterior: Releases trophic hormones (GH, TSH, ACTH, etc.). o Posterior: Secretes ADH and oxytocin. Feedback Control: o Negative: Maintains homeostasis by inhibiting upstream hormones. o Positive: Enhances secretion in specific cases (e.g., ovulation). Key Functions: o Regulates growth, metabolism, stress response, reproduction, and fluid balance.  Revision Table Target Gland/Organ/Physiological Effect of pituitary Hypothalamic Hormone Nuclei of Origin Target in Pituitary Pituitary Hormone hormone TRH (Thyrotropin- Paraventricular nucleus Anterior Pituitary TSH (Thyroid-Stimulating Thyroid gland – Stimulates synthesis and secretion of thyroid Releasing Hormone) (PVN) (Thyrotropes) Hormone) hormones and regulates thyroid cell proliferation and survival Adrenal cortex – Simulates synthesis and secretion of adrenal CRH (Corticotropin- Paraventricular nucleus Anterior Pituitary ACTH (Adrenocorticotropic cortex steroids (e.g.- cortisol) and proliferation and survival of Releasing Hormone) (PVN) (Corticotropes) Hormone) adrenal cortex cells Ovaries/Testes Ovaries/Testes––LH: LH:Females: Females,induces inducesovulation ovulationand and LH (Luteinizing Hormone), progesterone progesteronesynthesis. synthesis.Males: Males,gametogenesis and and stimulates synthesis GnRH (Gonadotropin- Anterior Pituitary Pre-optic nucleus secretion synthesis FSH (Follicle-Stimulating stimulates of testosterone, FSH: Females, and secretion stimulatesFSH: of testosterone. Releasing Hormone) (Gonadotropes) estrogen synthesis and promotes follicular growth. follicular Males, Hormone) Females: Stimulates estrogen synthesis, promotes promotes spermatogenesis growth Liver and other organs - Stimulates secretion of IGF-1 which is GHRH (Growth Hormone- Anterior Pituitary Arcuate nucleus GH (Growth Hormone) responsible for GH’s anabolic effects. Stimulates lipid and Releasing Hormone) (Somatotropes) CHO metabolism Anterior Pituitary Inhibits GH and TSH Somatostatin (GHIH) Periventricular nucleus Inhibitory action on growth and thyroid functions (Somatotropes) secretion PIH (Prolactin-Inhibiting Anterior Pituitary Arcuate nucleus Inhibits Prolactin secretion Mammary glands – Prevents milk production Hormone / Dopamine) (Lactotropes) Paraventricular nucleus Uterus – Stimulates contractions; Mammary glands – Oxytocin Posterior Pituitary Oxytocin (PVN) Stimulates milk ejection ADH (Antidiuretic Supraoptic nucleus Posterior Pituitary ADH Kidneys – Promotes water reabsorption Hormone / Vasopressin)  Recommended Reading Medical Sciences. Jeannette Naish. Chapter 10. Endocrinology and the Reproductive System. Or, Endocrine and Reproductive Physiology. Bruce White, John Harrison, Lisa Mehlmann. Chapter 5. Hypothalamus-Pituitary Complex Or, Master Medicine: Physiology. J McGeown. Chapter 8. Endocrine physiology.  Multiple Choice Question Which of the following best describes the primary function of the hypothalamus in endocrine regulation? A. Controlling the release of hormones from the adrenal glands B. Directly releasing hormones into the bloodstream to regulate body functions C. Orchestrating the release of pituitary hormones by producing and releasing regulatory hormones D. Synthesizing and storing hormones for the thyroid gland E. Temperature regulation and control of appetite Which hormone is released by the hypothalamus to stimulate the pituitary gland to release adrenocorticotropic hormone (ACTH)? A. Corticotropin-releasing hormone (CRH) B. Growth hormone-releasing hormone (GHRH) C. Gonadotropin-releasing hormone (GnRH) D. Prolaction-releasing hormone E. Somatostatin  Multiple Choice Questions Which of the following hormones is secreted by the posterior pituitary gland? A. Adrenocorticotropic hormone B. Anti-diuretic hormone C. Follicle-stimulating hormone D. Growth Hormone E. Thyroid-stimulating hormone Which one of the following hormones is secreted by somatotrope cells in the anterior pituitary? A. Adrenocorticotropic hormone B. Anti-diuretic hormone C. Follicle-stimulating hormone D. Growth hormone E. Thyroid-stimulating hormone