Anterior Pituitary Hormones PDF

Anterior Pituitary Hormones from the anterior pituitary are essential to regulate of the function of … Thyroid Glands Adrenal Glands Ovaries/Testis Mammary Glands Body Growth Viveiros | 2025 Topic outline 1. Cell types of the anterior pituitary gland 2...

Anterior Pituitary Hormones from the anterior pituitary are essential to regulate of the function of … Thyroid Glands Adrenal Glands Ovaries/Testis Mammary Glands Body Growth Viveiros | 2025 Topic outline 1. Cell types of the anterior pituitary gland 2. Major Hormones Produced (A-E-6) 3. Regulation of hormone synthesis and secretion Hypothalamic-pituitary vascular portal system Negative feedback loops 4. Three families of anterior pituitary hormones thyroid 5. Target glands and physiological function gland 6. Causes and consequences of pituitary gland dysfunction Anterior Pituitary (Adenohypophysis) (secretes 6 key hormones … A-E-6) 1. Prolactin (PRL) Mammary Gland: Milk production 2. Growth Hormone (GH) Bone, muscle, liver…etc. Stimulating hormones that act on other glands 3. Thyroid Stimulating Hormone (TSH) Thyroid Glands: Thyroxin (T4) & T3 4. Adrenocorticotropic Hormone (ACTH) Adrenal Cortex: Cortisol & Aldosterone 5. Follicle Stimulating Hormone (FSH) Ovary: Ovarian follicle development Testes: Sperm production 6. Luteinizing Hormone (LH) Ovary: Ovarian follicle ovulation Testes: Testosterone secretion Each hormone is produced by a different cell type of the anterior pituitary (… cells show a similar morphology) Distribution of different cells types within the anterior pituitary (labelled with different antibodies for different hormones) H & E staining only Somatotrope cells: produce Growth Hormone (GH) Lactotropes: Prolactin (PRL) Thyrotropes: Thyroid-stimulating hormone (TSH) Corticotropes: Adrenocorticotropic hormone (ACTH) Gonadotropes: Follicle-stimulating hormone (FSH) and “ Luteinizing hormone (LH) Synthesis and secretion of all anterior pituitary hormones are controlled by the hypothalamus PRH: Prolactin RH* Prolactin IH* (Dopamine) TRH: Thyrotopin RH* CRH: Corticotropin RH* GHRH: Growth Hormone RH* Growth Hormone IH* GnRH: Gonadotropin RH *RH: Releasing Hormone *IH: Inhibitory Hormone Hypothalamic control of the anterior pituitary Neurons in the hypothalamus produce and secrete Releasing and Inhibiting Hormones, which control the synthesis and release of anterior pituitary gland hormones 5 Releasing Hormones (RH) Prolactin releasing peptide (PRH) Growth hormone releasing hormone (GHRH) Hypothalamus Thyrotropin releasing hormone (TRH) Corticotropin releasing hormone (CRH) Releasing Inhibiting Gonadotropin releasing hormone (GnRH) Hormones Hormones (ON) (OFF) Anterior Pituitary 3 Inhibitory Hormones (IH) Gland Dopamine Growth Hormone inhibitory hormone (GHIH) Gonadotropin inhibitory hormone (GnIH) Target Glands/Tissues Hypothalamic neurohormones are carried directly to the anterior pituitary pituitary via the hypothalamic-pituitary portal system Involves two capillary beds connected by portal vessels (1) Allows for a rapid response (2) Little dilution of hormones secreted from the hypothalamus as these factors do not enter the general circulation Releasing/Inhibitory neurohormones are released from the neuronal axon endings into a capillary bed in the median eminence, then transported by the portal vessels to another capillary bed within the anterior pituitary Hypothalmic- hypophyseal portal system Hypothalamic-Pituitary Portal System Scanning electron micrograph of the hypothalamic-pituitary portal system (after vascular injection with latex) MHA: Media Hypophyseal Artery PPP: Primary Portal Plexus PV: Portal Vessels SHA: Superior Hypophyseal Artery P. Senger (2012) with permission from SPP: Secondary Portal Plexus Dr. H. Duvernoy, France  Anterior pituitary hormones target different glands and tissues Direct hormone action Regulates hormone synthesis & release Copyright © 2010 Pearson Education, Inc. Three families of anterior pituitary hormones (based on their structure) 1. Growth Hormone (GH) and Prolactin (PRL) Family** 2. POMC (pro-opiomelanocortin) Family Adrenocorticotrophic hormone (ACTH) 3. Glycoprotein Family Thyroid stimulating hormone (TSH) Gonadotrophins (FSH and LH) (1) Prolactin (PRL) Promotes mammary gland development and function (lactogenesis) Single chain (23KDa) protein Prolactin producing cells (pituitary tissue section) Member of a related protein family, which includes -Prolactin -Growth Hormone -Placental Lactogen Produced by the lactotroph cells in anterior pituitary Regulation of prolactin secretion (1) Inhibition of Prolactin Hypothalamus Dopamine released from neurons in the hypothalamus Dopamine PRH and TRH suppress prolactin synthesis and secretion from the anterior pituitary Anterior (3) Stimulation of Prolactin release Pituitary Gland Estrogen Prolactin releasing peptide (PRH) Prolactin Thyroid releasing hormone (TRH) from the hypothalamus Mammary Estrogen from the ovary Gland Stimulation of prolactin secretion Suckling, detected by mechanoreceptors in the nipple, inhibits dopamine (DA) release from the hypothalamus -and thereby promotes prolactin secretion (removal of the inhibitory signal) w Hypothalamusq DA s Anterior Posterior pituitary pituitary Prolactin (ng/ml) PROLACTIN OXYTOCIN milk gland myoepithelial cells cells Milk Synthesis Milk Ejection Minutes after washing the udder Prolactin promotes two major functions in the mammary gland (1) Mammary gland development: Increased alveolar number (2) Lactogenesis (milk production): Stimulates transcription of genes that encode milk proteins Mammary gland development (alveoli formation) * * Prl: Prolactin (2) Growth Hormone (GH)  Single chain (191aa) protein that is structurally similar to prolactin  Produced in the Somatotrope cells ~most abundant protein in the pituitary gland (10% of dry weight) ~secreted throughout life (after growth plates have fused), in a pulsatile manner (burst of secretion associated with the early hours of sleep)  Also referred to as Somatotropin Hypothalamus regulation of GH secretion (1) Growth hormone releasing hormone (GHRH) ~produced & released from the hypothalamus (2) Growth hormone inhibiting hormone (GHIH) ~also referred to as Somatostatin ~widely distributed in the CNS, GI tract and pancreas Growth Hormone Function GH stimulates Insulin Like Growth Factor-1 (IGF-1) from the liver (1) Promote protein deposition ~Facilitates amino acid (aa) transport (muscle) ~Increases transcription and translation ~Decreases protein & aa catabolism (2) Enhance fat utilization ~Increase lipolysis (increase acetyl-CoA) (3) Decrease carbohydrate metabolism ~Decreased glucose uptake* (may be GH direct action) (4) Stimulate bone and cartilage growth ~Increased protein deposition ~Stimulates osteoblasts *GH antagonizes insulin action (“diabetogenic effect”: decreased glucose uptake by cells & increase in blood) Growth Hormone Function (1) Acute Metabolic Effects ~Example …decreased glucose uptake (2) Long Term Body Growth Effects ~via IGF-1 (Insulin-like Growth Factor-1), but also dependent on Genetic potential Nutrition/health GH is essential throughout life Effects of GH disruption are related to developmental stage Bone epiphyseal growth plate Disruption of GH can lead to growth disorders (1) Growth Hormone Gigantism: Abnormal growth due to an excess of GH before the bone growth plates have fused Acromegaly: Abnormal growth due to an excess of GH, after the bone growth plates have fused Rare disorder (has been reported in older cats) Soft tissue growth: ~Enlarged paws and facial features ~Thickening of the skin ~Enlarged internal organs (heart, kidneys…) Expansion of the skull ~pronounced lower jaw protrusion with gaps J. Vet. Intern Med 2007: 21; 899 between teeth (and enlarged tongue) Causes: Pituitary Tumor that secretes GH Disruption of GH …. growth disorders (1) Growth Hormone Gigantism (proportional growth) Acromegaly (disproportionate growth) (2) Growth Hormone Dwarfism: Deficiency of growth hormone, before the bone growth plates have closed Causes: Pituitary tumor Need to distinguish from poor growth due to congenital hypothyroidism or Laron Dwarfism (GH receptor mutation) Pituitary Dwarfism in Dogs (German Shepherds) Underdevelopment of the pituitary gland Combined deficiency of several hormones -Growth Hormone (GH) -Thyroid stimulating hormone (TSH) (6 months) -Prolactin -Gonadotropins *ACTH hormone is not disrupted (?) A congenital problem (Genetic defect due to mutations on key transcription factors that regulate pituitary cell development) brother Common clinical manifestations growth retardation (.. proportionate) retention on secondary hairs (puppy coat) and alopecia (hair loss) Anterior Pituitary (Adenohypophysis) (secretes 6 key hormones … A-E-6) 1. Prolactin (PRL) Mammary Gland: Milk production 2. Growth Hormone (GH) Bone, muscle, liver…etc. Stimulating hormones that act on other glands 3. Thyroid Stimulating Hormone (TSH) Thyroid Glands: Thyroxin (T4) & T3 4. Adrenocorticotropic Hormone (ACTH) Adrenal Cortex: Cortisol & Aldosterone 5. Follicle Stimulating Hormone (FSH) Ovary: Ovarian follicle development Testes: Sperm production 6. Luteinizing Hormone (LH) Ovary: Ovarian follicle ovulation Testes: Testosterone secretion Three families of anterior pituitary hormones (based on their structure) 1. Growth Hormone (GH) and Prolactin (PRL) Family** 2. POMC (pro-opiomelanocortin) Family Adrenocorticotrophic hormone (ACTH) 3. Glycoprotein Family Thyroid stimulating hormone (TSH) Gonadotrophins (FSH and LH) (3) ACTH stimulates the adrenal cortex Q: If cortisol levels are high, what should the ACTH levels be in a normal patient? Want ACTH in respon Pituitary tumor that secretes ACTH can lead to Cushing’s (high cortisol) Three families of anterior pituitary hormones (based on their structure) 1. Growth Hormone (GH) and Prolactin (PRL) Family** 2. POMC (pro-opiomelanocortin) Family Adrenocorticotrophic hormone (ACTH) 3. Glycoprotein Family Thyroid stimulating hormone (TSH) Gonadotrophins (FSH and LH) (4) Thyroid Stimulating Hormone (TSH) Protein produced in the thyrotrope cells Also referred to as Thyrotropin Composed of 2 subunits (common -, and unique -chain) Alpha () S S Beta () Common -subunit in FSH, LH and TSH Unique -subunit is larger and confers biological specificity Thyroid Luteinizing Follicle Stimulating Hormone (LH) Stimulating Hormone (TSH) Hormone (FSH) TSH promotes thyroid hormone (T3/T4) synthesis & secretion Dopamine, IGF-1, Starvation Cold exposure TRH: Thyrotropin Releasing Hormone TSH: Thyroid Stimulating Hormone 1. Increased Metabolism 2. Growth and Development Disruption of TSH leads to thyroid disorders TSH: Increases thyroid hormone levels Hyperthyroidism ~rapid weight loss ~increased appetite, drinking and urination ~hyperactivity, ‘nervous’ behavior TSH: Reduces thyroid hormone levels ….. Hypothyroidism ~weight gain without increased food intake ~increased thirst & drinking ~lethargic behavior Hyper- and Hypothyroidism Tertiary Secondary Primary Disease can result from ‘disruptions’ in the function of the … ~Hypothalamus (3o) ~Pituitary (2o) most common ~Thyroid gland (1o) Consider both TSH and thyroid hormone levels Source of Pathology TSH T3 / T4 Conditions Hypothalamus/Pituitary High High Hyperthyroidism (Pituitary Tumor) Hypothalamus/Pituitary Low Low Hypothyroidism Thyroid Low High Hyperthyroidism (Thyroid tumor) Grave’s disease (Autoimmune disorder TSH-like antibodies activate TSH receptors) Thyroid High Low Hypothyroidism Hashimoto’s Thyroidism (Autoimmune) (5, 6) Gonadotropins … reproduction Follicle Stimulating Hormone (FSH) Luteinizing Hormone (LH) Both FSH and LH are produced in the Gonadotropes Glycoproteins composed of 2 subunits Alpha () S S S S Beta () Common -subunit in FSH, LH and TSH Unique -subunit is larger and confers biological specificity Thyroid Luteinizing Follicle Hormone Hormone Stimulating Hormone Gonadotropin (FSH and LH) Function (reproduction section) Females Males FSH ….stimulates FSH: Ovarian follicle development Spermatogenesis Inhibin/activin production Inhibin production Steroid hormone production Androgen binding protein production LH: LH: Oocyte ovulation Testosterone production Corpus luteum (CL) development Progesterone production Endocrine based disorders that are caused by anterior pituitary gland dysfunction Hyper- and Hypothyroidism: Disruption of TSH and Thyroid hormone Cushing’s Disease: ACTH and Cortisol Secondary Addison’s Disease: ACTH, Cortisol, Aldosterone Acromegaly and Dwarfism: Disruption of Growth Hormone (GH) Infertility / Delayed onset of Puberty: Disruption of gonadotrophins (LH & FSH) and sex steroid hormones (Estradiol, Terstosterone and Progesterone) Anterior pituitary hormone deficiency can result from ….. Isolated defect in the synthesis & secretion of a single hormone Panhypopituitary: Deficiencies in several hormones Traumatic injury to the pituitary Tumor that destroys pituitary cells or connection to the hypothalamus Leads to multiple problems in sexual maturation, adrenal and or thyroid function Pituitary Tumors (Adenomas) Non-metastatic* Interfere with normal synthesis & release of hormones Two main types of tumors Secretory: produce too much hormone Non-secretory: tumor cells do not produce hormones, but interfere with normal pituitary function Hypersecretion of hormones GH: Body growth disorders ACTH: Adrenals: Cushing’s Syndrome TSH: Thyroid: Metabolic disorders Prolactin: Prolactinoma (40% of all pituitary tumors in women) Hyposecretion of hormones Tumor mass effects: pressure on other areas of the brain Learning objectives (pituitary gland)  Know which tissues give rise to the pituitary gland during development  Understand the key differences between the posterior and anterior pituitary (neural vs. endocrine)  Explain how the hypothalamus regulates pituitary gland hormone synthesis and secretion (neural input, portal vasculature)  Explain feedback control of hormone secretion  Know the hormones secreted by the posterior pituitary gland (Oxytocin and ADH) and their function  Know the hormones secreted by the anterior pituitary gland (GH, Prolactin, ACTH, TSH, FSH and LH) and their function  Describe how disruptions in pituitary gland function can lead to specific endocrine disorders