Introduction to the Hypothalamic-Pituitary Axis - Student Copy(1).pptx

Introduction to the HypothalamicPituitary Axis BSMS203: Theme 1, Lecture 3 Oliver Steele [email protected] Join at slido.com Lecture in Context This lecture will build on … … by introducing and covering … Introduction to Endocrinolog y You are here! • A LOT more feedback • Feedback loops an...

Introduction to the HypothalamicPituitary Axis BSMS203: Theme 1, Lecture 3 Oliver Steele [email protected] Join at slido.com Lecture in Context This lecture will build on … … by introducing and covering … Introduction to Endocrinolog y You are here! • A LOT more feedback • Feedback loops and self regulation within the endocrine system Series of Endocrine Physiology Lectures 2 loops that form the hypothalamicpituitary axis • Physiology of the anterior and posterior lobe of the pituitary • Associated pathophysiology Intended Learning Outcomes To gain a basic understanding of the physiology of the hypothalamic-pituitary axis and its assessment. 3 Outline 1. Anatomy of the Hypothalamic-Pituitary Axis • Structure, blood supply and nervous innervation 2. Physiology of the Anterior Lobe of the Pituitary Gland • Overview of the hormones produced by the anterior lobe Feedback loops associated with eachofhormone 3. • Physiology of the Posterior Lobe the Pituitary Gland • Overview of the hormones produced by the posterior lobe Feedback loops associated with each hormone 4. • Pituitary Pathophysiology & Treatment • Imaging with MRI/CT • Adenomas, Cushing Syndrome and Acromegaly / Gigantism • Visual and hormonal assessment 4 Anatomy of the Hypothalamic-Pituitary Axis Section 1 of 4 Anatomy of the HPA Below the corpus callosum is the thalamus Below the thalamus is the hypothalamus The pituitary stalk (infundibulum) connects the hypothalamus to the pituitary gland The HypothalamicPituitary Axis (HPA) is near the optic chiasm 6 Mid-sagittal view of the brain Anatomy of the HPA Hypothala mus Infundibul Optic um Chiasm Pituitary gland is encased in sphenoid bone offering further protection Pituitary gland is sub-divided into two functionally and anatomically distinct regions • Posterior Pituitary (neurohypophysis) • Anterior Pituitary (adenohypophysis) Sphenoi Anteriord Bone Posterior (adeno(neurohypophy hypophysis) sis) 7 Blood Supply to the HPA Blood supply from the internal carotid artery via superior & inferior hypophysial arteries Hypophyseal portal system Hypothala mus Primary plexus then drains down the long portal veins into the secondary plexus Connection between two plexuses of capillaries is termed a portal system Primary Plexus Superior hypophysial artery Long Portal Veins Sinusoidal capillaries have Secondary Plexus fewer tight junctions which facilitates the easier Veinous drainage movement of large molecules Anterior Infundibulu m Inferior hypophysial artery Veinous drainage Posterior 8(adenohypophys (neurohypophy Nervous innervation to the HPA Originating from the hypothalamus, neurosecretory terminals release hormones The posterior lobe receives direct innervation from the terminals of the paraventricular and supraoptic nuclei The anterior lobe doesn’t receive direct innervation Projections from the arcuate nucleus release hormones into the primary plexus Paraventricular & Supraoptic Nuclei Hypothala mus Arcuate Nucleus Infundibulu m Anterior Posterior 9(adenohypophys (neurohypophy Long portal veins are present in which region of the hypothalamic-pituitary axis? 1. 2. 3. 4. Hypothalamus Anterior lobe Posterior lobe Infundibulum Correct Answer: Infundibulum Move to reveal answer 1 Answer Slide Blood supply from the internal carotid artery via superior & inferior hypophysial arteries Hypothala mus Primary plexus then drains down the long portal veins into the secondary plexus Connection between two plexuses of capillaries is termed a portal system Sinusoidal capillaries have fewer tight junctions, and allow for easier movement of larger molecules Primary Plexus Superior hypophysial artery Long Portal Veins Secondary Plexus Veinous drainage Infundibulu m Inferior hypophysial artery Veinous drainage Anterior Posterior 1 (adenohypophys (neurohypophy Anterior Pituitary Gland: Hormones, pathways & cell types Section 2 of 4 Hypophysial Releasing Hormones Neurosecretory terminals from the arcuate nucleus secrete releasing hormones into the primary plexus Releasing hormones promote the production of stimulating (trophic) hormones from the anterior pituitary gland Hypothala mus Arcuate Nucleus Primary Plexus Long Portal Veins Secondary Plexus Stimulating hormones enter general circulation via venous drainage Veinous drainage Circulation in blood supply 1 (endocrine) Anterior (adenohypophys is) Infundibulu m Growth Hormone - Physiology Effect Target Tissue Growth Hormone Releasing Hormone (GHRH) promotes the release of Growth Hormone (GH) • Liver Secretion of IGF-1 • Increased glycolysis Bone & Muscle • Increased muscle mass • Increased bone length & density • Increased lipolysis • Decreased glucose GH is secreted from somatotropes in the anterior pituitary gland Somatostatin is the negative equivalent for GH Hyperproduction • Acromegaly & Gigantism Adipose Tissue 1 Growth Hormone - Regulation Behavioural Sleep Fasting Exercise Hypothalamus SS Releasing Hormone Pituitary (Anterior) GHRH - GH Trophic Hormone Liver Bone & Muscle Target Tissue IGF-1 1 Long-loop Inhibition Short-loop Inhibition Adipose Tissue ACTH - Physiology Target Tissue Corticoptrophin releasing hormone (CRH) promotes the release Adrenal of adrenocorticotrophic hormone Glands (ACTH) ACTH is secreted from corticotropes in the anterior pituitary gland Liver ACTH stimulates the adrenal glands to Muscle release cortisol – referred to as the ‘stress hormone’ Hyperproduction • Cushing Syndrome Immune System 1 Effect • Cortisol secretion • Increased gluconeogenesis • Increased protein degradation • Immune suppression ACTH - Regulation Hypothalamus Behavioural Exercise Stressors Various neuronal signals Releasing Hormone CRH Pituitary (Anterior) - Longloop Inhibitio n ACTH Adrenal Glands Trophic Hormone Liver Bone & Muscle Immune System Short-loop Inhibition Target Tissue 1 Cortisol Thyroid stimulating hormone - Physiology Thyrotropin releasing hormone (TRH) promotes the release of Thyroid stimulating hormone (TSH) Target Tissue Thryoid TSH is secreted from thyrotropes in the anterior pituitary gland • T3 & T4 Secretion • Master regulator of metabolic rate Secreted T3/T4 is 80% T4 : 20% T3 • T4 is converted to T3, so is therefore considered ‘inactive’ Disrupted thyroid physiology Effect • Elevated heart rate 1 • Increased body temp. Thyroid stimulating hormone - Regulation Hypothalamus TRH Releasing Hormone Pituitary (Anterior) TSH Trophic Hormone Target Tissue Most Cell Types Master regulator of metabolic rate 1 Longloop Inhibitio n Thyroid Short-loop Inhibition T3 & T4 Luteinizing & Follicle Stimulating Hormones Gonadotrophin releasing hormone (GnRH) promotes the release of Luteinizing hormone (LH) and follicle stimulating hormone (FSH) • Ovaries LH & FSH is secreted from gonadotropes in the anterior pituitary gland • • • Testes Typically maintained through classical negative feedback unless the background environment changes, ie ovulation etc. Effect Target Tissue 2 • Follicular Growth Ovulation Production of 17β-oestradiol, progesterone Production of testosterone Maturation of sperm LH/FSH - Regulation Hypothalamus Releasing Hormone GnRH GnRH Pituitary (Anterior) Trophic Hormone - LHFSH - LHFSH Target Tissue Ovaries Estrogen Progesterone 2 Testes Testosterone Prolactin - Physiology Prolactin is produced by lactotropes in the anterior pituitary gland Dopamine (DA) inhibits lactotropes Suckling behaviour activates mechanorecptors and afferent neuronal pathways to inhibit dopamine production  Prolactin secretion Primary function is the production of milk in the Effect Target Tissue Breast Alveoli 2 • Milk Production Prolactin - Regulation Hypothalamus Pituitary (Anterior) Trophic Hormone Target Tissue Short-loop Inhibition DA Releasing Hormone - + Afferent multineural pathway Prolactin Suckling activates mechanoreceptors 2 Breast Alveoli Cell Types of the Anterior Pituitary Prevalence (%)Stimulated by Produces (thyrotropes) 5% TRH TSH (somatotropes) 50% GHRH GH (lactotropes) 10-20% PrRP (DA) Prolactin (gonadotropes) 10-15% GnRH LH, FSH (corticotropes) 5-10% CRH ACTH 2 Secretion of IGF-1 is promoted by which hormone? 1. 2. 3. 4. Growth hormone Somatoastatin Growth hormone releasing hormone Adrenocorticotrophic hormone Correct Answer: Growth Hormone Move to reveal answer 2 Growth Hormone - Regulation Behavioural Sleep Fasting Exercise Hypothalamus SS Releasing Hormone Pituitary (Anterior) GHRH - GH Trophic Hormone Liver Bone & Muscle Target Tissue IGF-1 2 Long-loop Inhibition Short-loop Inhibition Adipose Tissue Posterior Pituitary Gland: Hormones & pathways Section 3 of 4 Posterior Lobe Nerve Terminals Posterior pituitary is much less glandular than the anterior pituitary Paraventricular & Supraoptic Nucleus Neurosecretory terminals from the paraventricular and supraoptic nuclei secrete stimulating (trophic) hormones Hypothala mus Descending Axons Infundibulu m Veinous drainage Stimulating hormones secreted into the plexus of capillaries then enters circulation 2 Posterior (neurohypophysi s) Circulation in blood supply (endocrine) Oxytocin Secreted from neurosecretory terminals of projecting axons from the supraoptic (SO) and paraventricular (PV) nuclei Effect Target Tissue Breast Alveola r Epitheli al Cells Mechanoreceptor activation triggers the SO and PV nuclei to produce oxytocin • Milk Ejection • Muscular contractions during childbirth Circulating levels are very low, and spike due to positive feedback mechanisms Uterus Primary function is targeted muscle contractions, yet has interesting effects in the reward pathways in the brain 2 Oxytocin Regulation Hypothalamus Pituitary (Posterior) Trophic Hormone Afferent multineural pathway Afferent multineural pathway + Breast alveolar epithelial cells Target Tissue Downstream Effect + Oxy Suckling activates mechanoreceptors Muscle Contraction 3 Uterus Cervical pressure activates mechanorecep tors Antidiuretic Hormone Antidiuretic hormone (ADH) is secreted by neurosecretory terminals of projecting axons from the supraoptic (SO) and paraventicular (PV) nuclei Effect Target Tissue Kidneys Antidiuretic hormone (ADH) impairs the kindey’s filtering of bodily fluids (diuresis), thus retaining water. Secretion is regulated by osmoreceptors that respond to the amount of water in the blood • Water retention • Sweat reduction Sweat Glands Low osmolarity = more water in blood High osmolarity = less water in blood 3 Antidiuretic Hormone Hypothalamic Osmoreceptors Hypothalamus + Higher Osmotic Pressure (less water in blood) Pituitary (Posterior) - Trophic Hormone Target Tissue Downstream Effect Lower Osmotic Pressure (more water in blood) ADH Kidneys Sweat Glands 3 Water Retention Posterior & Anterior Interplay Hypothalamus Releasing Hormone GnRH DA Anterior Posterior Pituitary + Trophic Hormone FSH, LH Prolactin Ovaries Target Tissue Oxytocin Breast alveolar epithelial Cells Suckling activates mechanoreceptors 3 Secretion of IGF-1 is promoted by which hormone? 1. 2. 3. 4. Growth hormone Somatostatin Growth hormone releasing hormone Adrenocorticotrophic hormone Correct Answer: Growth Hormone Move to reveal answer 3 Answer Slide Hypothalamus Pituitary (Posterior) Trophic Hormone Afferent multineural pathway Afferent multineural pathway + Breast alveolar epithelial cells Target Tissue Downstream Effect + Oxy Suckling activates mechanoreceptors Muscle Contraction 3 Uterus Cervical pressure activates mechanorecep tors Pituitary Pathophysiology Section 4 of 4 MRI and Pituitary Imaging CT Scan Pituitary is located deep within the brain, so visual assessment is challenging MRI offers vast resolution improvements over CT MRI Normal 3 MRI – Pituitary Tumour Pituitary Adenoma TSHomas VERY rare Thyrotoxicosis GH-Secreting Tumours Too much Growth Hormone Acromegaly & Gigantism Prolactinomas Galactorrhea Reduced gonadal function FSH/LH Secreting Tumours Rare Hypersecretion syndromes ACTH-Secreting Tumours Too much ACTH Cushing’s Syndrome Note: Not always secretory (functional), can cause problems due to mass (non-functional) 3 Pituitary Cushing Syndrome Corticotrope Adenomas result in hypersecretion of ACTH that don’t respond to the normal negative feedback loops ACTH hypersecretion results in chronically elevated Cortisol ACTH-Adenoma Symptoms • High Blood Pressure  Red cheeks • Excessive weight gain  ‘Moon Face’, Normal Function Truncal Obesity Thin Extremities Treatments • Surgical removal (transsphenoidal surgery) • Radiation therapy 3 Pituitary Cushing Post Surgery Acromegaly & Gigantism Somatotrope Adenoma causes hypersecretion of Growth Hormone Gigantism = Childhood GH Hypersecretion Acromegaly = Adulthood GH Hypersecretion Diagnosis • Measure IGF-1 or GH levels and MRI Treatment Acromegaly • Surgical/radiation removal ideally 4 Gigantism Pituitary Tumours and Optical Disruption Visual Pathway Visual Defect 1 1 2 2 Example of Lesion Left Optic Nerve Compression Chiasmal compression from a pituitary tumour (bitemporal hemianopia ) 3 3 4 Left Cerebrovascular Event Used to assess integrity of the hypothalamicpituitary-adrenal axis Hypoglycaemia should induce spikes in cortisol and growth hormone Poorly tolerated in children Requires close monitoring to avoid shock/diabetic coma Serum GH Plasma CortisolPlasma Glucose (mmol/l) (mmol/l) (mmol/l) Insulin Tolerance Testing Insuli n 5 Deliv ery Normal Insuli n Deliv 5 ery 3 3 1 1 800 800 600 600 400 400 200 200 40 40 2 0 10 20 Hypopituitary 10 <2 0 60 Time (minutes) 4 < 120 2 0 60 Time (minutes) 120 Pituitary Cushing Syndrome is initially caused by excessive secretion of what? 1. 2. 3. 4. Cortisol Corticotrophin releasing hormone Adrenocorticotrophic hormone Corticotropes Correct Answer: Adrenocorticotrophic hormone Move to reveal answer 4 Answer Slide Corticotrope Adenomas result in hypersecretion of ACTH that don’t respond to the normal negative feedback loops ACTH hypersecretion results in chronically elevated Cortisol ACTH-Adenoma Symptoms • High Blood Pressure  Red cheeks • Excessive weight gain  ‘Moon Face’, Normal Function Truncal Obesity Thin Extremities Treatments • Surgical removal (transsphenoidal surgery) • Radiation therapy 4 Pituitary Cushing Post Surgery What you need to know • Understand structure, blood supply, and nervous innervation of the hypothalamus and pituitary gland • Appreciate the different hormones secreted by the anterior and the posterior lobe of the pituitary gland, their broad function and the control of their secretion via feedback loops • Appreciate the advancements in imaging of pituitary adenomas with MRI • Understand the range of impacts disruption to the hypothalamic-pituitary axis can have • 4 Suggested Additional Reading Greenspan’s Basic and Clinical Endocrinology. “Chapter 4 is a good place to start here, however further reading on the respective pathways and feedback loops can be found in further chapters.” Tenth Edition. Gardner & Shoback. McGraw-Hill Medical; 2018. ISBN: 978-0071622431. “Chapter 3 and 4 succinctly describes the different feedback loops described here.” Integrated Endocrinology First Edition. Laycock & Meeran. Wiley-Blackwell; 2013. ISBN: 978-0470688120. 4 Feedback Opportunity If you have any feedback for me on this lecture, please either scan the QR code or follow the link below Questionnaire is short (~2 mins) and anonymous All feedback helps me to improve, and as a result improve the quality of your teaching. https://universityofsussex.eu.qualtrics.com/jfe/form/SV_3wVeRAhOFt bXjee Help me help you! 4