Microanatomy of the Endocrine System 1 PDF

Microanatomy of the endocrine system 1 Dr Diana Bochynska, DVM, Dipl. ECVP This presentation has been developed and adapted from previous versions compiled by Dr M Valentine, Drs A Kessell, M...

Microanatomy of the endocrine system 1 Dr Diana Bochynska, DVM, Dipl. ECVP This presentation has been developed and adapted from previous versions compiled by Dr M Valentine, Drs A Kessell, M Dennis, L Bogdanovic and C Fuentealba Figures and diagrams are from the sources were indicated or from the recommended texts that accompany the course This presentation is for educational purposes at Ross University School of Veterinary Medicine only  Endocrine 1 Learning objectives 1. List the primary endocrine organs. Explain the importance of the hypothalamus. Define: neurosecretory neuron, conducting neuron. Describe the origin of the two parts of the hypophysis. Name the cells of the adenohypophysis and the hormones produced by them. Name the main parts of the adenohypophysis and the neurohypophysis. Explain function of the hypothalamic-hypophyseal portal system. Give the location and function of the pineal gland. List the common types of hormones and their intracellular method of action. 2. Trace a releasing hormone from the hypothalamus to the acidophils/basophils of the adenohypophysis, then to the appropriate target organ for each, and the production of the third hormone of each (where applicable) and state the effect of the terminal hormone. 3. Trace the production of oxytocin/antidiuretic hormone (ADH) from the hypothalamus to its target cells and action on the mammary gland/kidney. 4. List the hormone-producing cells of the thyroid/parathyroid glands and their basic actions on the body. 5. List the regions of the adrenal gland, the hormones produced there, and their general action on the body. Identify in tissue sections the regions of the adrenal gland. 6. List the hormones of the pancreatic islets, kidney, and their general effects. List some hormones produced by GI tract enteroendocrine cells. 7. Be able to recognize in section: hypophysis, adenohypophysis, acidophils, basophils, chromophobes, melanotrophs, neurohypophysis, thyroid/parathyroid gland, follicular cells, parafollicular cells; adrenal gland, its zones and cell products; endocrine pancreatic cells.  Endocrine 1 Features of endocrine glands Endocrine glands are ductless glands that secrete HORMONES (c.w. exocrine glands) into the circulation Highly vascular Hormones circulate within the body via the bloodstream to affect cells at distant SPECIFIC TARGET ORGANS  Endocrine 1 Hormones are signaling molecules Cell signaling Originally all hormones were thought to only utilize endocrine signaling Autocrine- stimulate or inhibit self Paracrine- stimulate or inhibit adjacent cell Endocrine- stimulate distant target cell  Endocrine 1 Endocrine hormones travel via the blood stream to target cells Hormones usually operate in a feedback loop Releasing Hormones Stimulating Hormones  Endocrine 1 Primary endocrine organs The endocrine system is composed of endocrine organs, as well as tissues and cells found in small numbers in nonendocrine organs. Pituitary gland (hypophysis cerebri) Pineal gland (epiphysis cerebri) Thyroid glands Parathyroid glands Adrenal glands Secondary organs can also secrete hormones, but it is not the primary function e.g. ovaries, testes, kidneys, liver, pancreas etc. MAJOR ENDOCRINE ORGANS FUNCTIONS Internal environment Energy production, storage, and utilization Reproduction Growth & development  Endocrine 1 1. Integrates nervous system and endocrine system (neurosecretory neurons) 2. Involved in homeostasis 3. Receives signals from all parts of brain, special senses and spinal cord 4. Blood brain barrier absent (allowing hypothalamic neurons to easily respond to ionic and molecular The HYPOTHALAMUS signals (importantly, hormonal signals) in the blood).  https://doi.o rg/10.3389/fendo.2017.00275 Neurosecretion is defined as the synthesis and storage of neuropeptides in brain neurons and their release from axonal Transmission electron microscopy images of terminals into the circulation. secretory vesicles in growth hormone cells of porcine pituitary. DOI:10.1177/153537020422900707 Neurosecretory cells resemble non-neural endocrine cells in their actions; They release hormones into the circulation For interest only and regulate several physiological responses.  E n d o c r i n e 1 http://vanat.cvm.umn.edu/mriBrainAtlas/MRIBrainTransAtlas.ht ml  Endocrine 1 Abbreviations – just a reminder Growth hormone–releasing hormone (GHRH) (somatotropin- releasing hormone [SRH]) Gonadotropin-releasing hormone (GnRH) Prolactin-releasing factor (PRF) Thyrotropin-releasing hormone (TRH) Corticotropin-releasing hormone (CRH) Adrenocorticotropic hormone (ACTH) Antidiuretic hormone (ADH), also called arginine vasopressin (AVP)  Hypothalamus ADH GnRH, GHRH, OTC TRH, CRH, PRF HYPOTHALAMO- RELEASING PITUITARY AXIS HORMONES AND PORTAL SYSTEM Adenohypophysis Neurohypophysis STIMULATING HORMONES Collecting vein  Hypothalamus neurosecretory neurons GnRH ADH OXYTOCIN Releasing GHRH hormones via TRH hypophyseal CRH portal system PRF Adenohypophysis Neurohypophysis Stimulating hormones via Direct secretion into systemic circulation systemic circulation ACTH FSH/LH TSH GH PRL ADH OXYTOCIN ACT ON TARGET EFFECTOR ORGANS Hypothalamo-pituitary-peripheral target organ axis Vasopressin (ADH) kidney HYPOTHALAMUS Oxytocin mammary gland and uterus Hypothalamic releasing hormones anterior pituitary stimulating hormones (1) ACTH adrenal cortex (2) TSH thyroid gland (3) GH liver, muscle, bone (4) and (5) LH/FSH gonads (6) PRL mammary gland (and corpus luteum in canines) (7) Hypothalamus, (8) adenohypophysis, (9) hypophyseal cleft, (10) neurohypophysis. Dellman’s histology book  Ventral brain: Pituitary Pyriform lobe gland Pons Rostral  Endocrine 1 The hypothalamus is closely associated to the pituitary gland Pituitary gland = 2 parts Anterior pituitary /adenohypophysis Pars distalis Pars intermedia Pars tuberalis Posterior pituitary/ neurohypophysis Infundibulum Pars nervosa THE PITUITARY GLAND DEVELOPS FROM ECTODERM AND NEUROECTODERM THE PITUITARY GLAND H O P Located ventral to hypothalamus (H), near AP PP optic chiasm (O) Lies in hypophyseal fossa of sella turcica (ST) ST Pituitary gland (P) = 2 parts Wheater’s Functional Histology Anterior pituitary or adenohypophysis (AP) Posterior pituitary or neurohypophysis (PP) O Anterior pituitary envelops posterior pituitary H P AP PP Anterior pituitary : adenohypophysis Derived from epithelium / ectoderm of oral cavity/pharynx 3 parts Pars distalis Pars tuberalis Tube like around infundibulum Pars intermedia (POMC) In between neurohypophysis and pars distalis Hypophyseal cavity/cleft is the remnant of Rathke's pouch  Pars distalis of the pituitary gland The cells of the pars distalis have been classified as acidophils, basophils, or chromophobes. They vary in size, shape, number, and position depending on species, sex, age, and physiologic status (e.g., during pregnancy and lactation or after gonad removal). Five subtypes of cells have been further identified with immunohistochemistry. Each cell type (called a “-troph”) expresses a peptide, protein, or glycoprotein hormone (called a tropin) and represents a definitive and terminal differentiation.  Adenohypophysis: Pars distalis in H&E stain Chromophils (stimulating hormones) Acidophils (GH, PRL) Basophils (ACTH, TSH, FSH, LH) Chromophobes (C) Sinusoids (S) H&E Junqueira’s Basic Histology, 2010  Endocrine 1 Acidophils Specifically, somatotrophs that synthesize and secrete growth hormone (GH) are concentrated laterally in the pars distalis; Lactotrophs, which produce prolactin (PRL), Lactotroph cell size and dye affinity increase during pregnancy and lactation. (Alcian Blue, Orange G, Schiff’s Reagent). 1. Acidophil 2. Basophil 3. Chromophobes 8. Sinusoid  Endocrine 1 Basophils Thyrotrophs produce thyroid-stimulating hormone (TSH), are more numerous midventrally, Gonadotrophs coexpress follicle-stimulating hormone (FSH) and luteinizing hormone (LH), are relatively small, Corticotrophs produce adrenocorticotropic hormone (ACTH) and are uniformly dispersed in the pars distalis. These cells are less conspicuous within the parenchymal cell clusters and are difficult to identify (Alcian Blue, Orange G, Schiff’s Reagent). with the light microscope. Corticotrophs may be 1. Acidophil spherical, ovoid, or stellate, depending on the species. 2. Basophil Their basophilic granules stain with antibody for both 3. Chromophobes ACTH and -lipotropin hormone. 8. Sinusoid *Adrenocorticotropic hormone (ACTH) is a tropic hormone produced by the anterior pituitary. The hypothalamic- pituitary axis controls it. ACTH regulates cortisol and androgen production.  Endocrine 1 Chromophobes Chromophobes stain poorly with dyes used to identify acidophils and basophils. Some are considered postsecretory acidophils and basophils. Still other stellate-shaped chromophobes are interspersed between the other cells of the pars distalis, and it has been suggested that (Alcian Blue, Orange G, Schiff’s Reagent). they may represent an undifferentiated stem 1. Acidophil cell of the adenohypophyseal parenchyma. 2. Basophil 3. Chromophobes 8. Sinusoid Adenohypophysis: Pars distalis immunohistochemical stain for Luteinizing Hormone (LH) Cells in the anterior pituitary are difficult to differentiate based on H&E stains Immunohistochemical (IHC) stains have been developed to identify the cells Antibodies attach to LH and then a secondary stain that is easy to visualize is applied Neoplasia and research Hormones of the hypothalamo- HYPOTHALAMUS pituitary axis Clusters of neurosecretory neurons (paraventricular Releasing hormones and supraoptic nuclei) that monitor HOMEOSTASIS GnRH RELEASING HORMONES GHRH TRH GnRH, TRH, CRH, GHRH, PRF CRH PRF ADH and OXYTOCIN ACTH The pituitary gland secretes STIMULATING HORMONES PITUITARY Stimulating hormones via systemic circulation GH PRL Adenohypophysis: pars intermedia Species differences in size Lies between pars nervosa and pars distalis Contains large pale cells produce large molecule proopiomelanocortin (POMC) POMC cleaved into endorphins, melanotropins and lipotropins PITUITARY GLAND: ADENOHYPOPHYSIS: PARS INTERMEDIA Inter- PI PN glandular cleft PN 40x Remnant of Rathke’s 1000x pouch cavity  Endocrine 1 PARS INTERMEDIA Varies between species Melanotrophs are the most abundant parenchymal cell of the pars intermedia, secreting -melanocyte-stimulating hormone and lipotropin. These peptide hormones are processed products of POMC expressed by the melanotrophs. Hypothalamic axons terminate in the pars intermedia and include dopaminergic, serotoninergic, adrenergic, and GABAergic axons that modulate the activity of the parenchyma. 1. Acidophils 2. Blood vessel 3. Cavity of Rathke’s pouch 4. Chromophobes 5. Follicle 6. Infundibular cavity 7. Pars distalis 8. Pars intermedia 9. Pars nervosa 10. Pars tuberalis  Pars Tuberalis The pars tuberalis is composed of cell clusters that form a folded tissue with occasional small cysts. The parenchymal cells of the pars tuberalis have melatonin receptors and are believed to regulate the seasonal reproductive cycle of some domesticated mammals. 2. Ependymal cells 3. Follicle 4. Infundibular cavity 5. Infundibular stalk 10. Pars tuberalis  Endocrine 1 Neurohypophysis: posterior pituitary Derived from NEUROECTODERM 2 parts Pars nervosa Infundibulum Stores hormones made in hypothalamus for release directly into blood stream Antidiuretic hormone (ADH) Oxytocin  Endocrine 1 Neurohypophysis The neurohypophysis contains the axons of hypothalamic neurons and central gliocytes (“pituicytes”), but no neuron cell bodies. The neuron cell bodies in the hypothalamus and secretory granules in their axons stain positively with antibody to oxytocin (OT) and antidiuretic hormone (ADH). ADH-producing neurons and OT-producing neurons are present in both the supraoptic nuclei and the paraventricular nuclei. Secretory vesicles containing the hormone are transported along microtubules to axon terminals near blood capillaries in 1. Cavity of Rathke’s pouch 7. Pars distalis the neural lobe. 8. Pars intermedia 9. Pars nervosa Along the course of the axon, secretory vesicles form focal accumulations (Herring bodies); when stained with aldehyde- fuchsin, these can be resolved by light microscopy.  Hypothalamus neurosecretory neurons GnRH ADH OXYTOCIN Releasing GHRH hormones via TRH hypophyseal CRH portal system PRF Adenohypophysis Neurohypophysis Stimulating hormones via Direct secretion into systemic circulation systemic circulation ACTH FSH/LH TSH GH PRL ADH OXYTOCIN ACT ON TARGET EFFECTOR ORGANS  Endocrine 1 Neurohypophysis : pars nervosa Unmyelinated nerve fibers (neurosecretory) Herring bodies (H) store ADH and oxytocin Pituicytes Indistinct on H&E Provide support Dellman’s histology book The following slides are from your histology book with highlighted important information.  Endocrine 1 Growth hormone–releasing hormone (GHRH) (somatotropin- releasing hormone [SRH]) is released from neurons of the arcuate nucleus in response to neural stimulation (e.g., during sleep and exercise). It binds to its receptor on the somatotrophs of the pars distalis. “ GH targets all cells, but especially hepatocytes, skeletal myocytes, adipocytes, and growth plate chondrocytes. GH induces an anabolic effect in muscle; in liver and cartilage, GH induces synthesis and release of insulin like growth factor I (IGF-I; somatomedin). IGF-I mediates additional GH effects by acting on chondroblasts, promoting their proliferation and thus causing growth of the skeleton. GH causes its own downregulation (negative feedback) by stimulating somatostatin producing neurons in the hypothalamus. Growth hormone  Endocrine 1 Prolactin-releasing factor (PRF) remains poorly understood. Prolactin (PRL) is principally regulated by tonic inhibition provided by dopamine from the hypothalamus. “ PRL targets its receptor on epithelial cells of the mammary gland -> stimulates proliferation and differentiation of the epitheliocytes as milk-synthesizing cells. Further, PRL binds to its receptor on dopaminergic neurons of the hypothalamus, increasing dopamine synthesis and release, thus causing inhibition of PRL release in the pars distalis. Together with GH, PRL also stimulates the immune system, specifically the proliferation and differentiation of lymphocytes. Prolactin  Endocrine 1 Thyrotropin-releasing hormone (TRH) is released from small neurons in the paraventricular nucleus and binds to its GPCR on thyrotrophs. “ thyroid-stimulating hormone (TSH; thyrotropin). stimulating the synthesis and storage of thyroglobulin and the release of thyroid hormones, triiodothyronine (T3) or tetraiodothyronine (T4). In turn, negative feedback of T3 or T4 to the hypothalamus and the pars distalis regulates the production of TRH and TSH, respectively. Thyrotropin-releasing hormone thyroid-stimulating hormone one (TRH)  Endocrine 1 Gonadotropin-releasing hormone (GnRH) is a protein hormone released from neurons diffusely scattered in the hypothalamus; Leads to release of the glycoprotein hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH). “ In the female, FSH binds to receptors on the follicular epithelial cells; in the male, FSH binds to its receptors on sustentacular cells (Sertoli cells) of the testis. In both sexes, production of estrogen is signaled by FSH. In the female, LH binds to internal thecal cells, signaling the production of testosterone, and on follicular and thecal cells of the postovulatory follicle, signalling production of progesterone. Cells of the ovarian interstitial stroma in the pig, dog, cat, rabbit, and human also produce testosterone. In the male, LH (also called interstitial cell–stimulating hormone [ICSH]) binds to its receptor on the interstitial cells (Leydig cells) and signals production of testosterone. In addition to effects on other target cells, these gonadal steroids bind to cells of the hypothalamus and the pars distalis, negatively regulating production of GnRH and gonadotropins. FSH also stimulates follicular cells, corpus luteal cells, and sustentacular cells to synthesize inhibin and activin. Gonadotropin-releasing hormone (GnRH) Corticotropin-releasing hormone (CRH) is a protein hormone released from small neurons in the paraventricular nucleus in response to neural signaling. CRH binds to its receptor on the corticotrophs, elevating intracellular concentration of cAMP and triggering calcium-mediated exocytosis of secretory vesicles containing adrenocorticotropic hormone (ACTH). “ ACTH binds to its receptor on adrenal cortical parenchymal cells and, via adenylate cyclase and cAMP, activates proteins that increase transcription of the enzymes involved in steroid hormone biosynthesis (e.g., glucocorticoids). Glucocorticoids negatively regulate CRH production in the hypothalamus and negatively regulate POMC synthesis and ACTH release in the pars distalis. In response to stress, signals creating increased neurogenic input to the hypothalamus overcome this inhibition of ACTH by glucocorticoid Corticotropin-releasing hormone (CRH) THE PINEAL GLAND  Endocrine 1 Pineal Gland The pineal gland resembles pinecone Pinealocytes secrete MELATONIN Blood vessels Neuroglial supporting cells Responds to stimuli detected in the retina Darkness stimulates pinealocyte secretion of MELATONIN --> circadian 24 hr rhythm Regulates rhythms of bodily activity Seasonal reproduction Long day and short-day breeders  Endocrine 1 Pineal gland histology 3. Fibers of neuroglial cells 4. Follicle 10. Pineal gland 11. Pineal stalk 12. Pinealocytes  Pinealocytes (with melanin pigment) Corpora arenacea (brain sand) Slide 67 1000x Pineal Gland By Mikael Häggström, M.D.-