What are the main hormone products of the Thyroid Gland
Tetraiodothyronine (T4)
Triiodothyronine (T3)
Calcitonin (CT)
What are the main hormone products of the Parathyroid Gland
Parathyroid Hormone (PTH)
What are the main hormone products of the Pineal Gland
Melatonin
What are the main hormone products of the Thymus
Thymosin
What are the main hormone products of the Heart
Atrial Natiuretic Peptide (ANP)
Brain Natiuretic Peptide (BNP)
What are the main hormone products of the Adrenal Cortex
Glucocorticoids
Mineralcorticoids
Androgens
What are the main hormone products of the Adrenal Medulla
Epinephrine
Norepinephrine
What are the main hormone products of the Pancreas
Insulin
Glucagon
Somatostatin
Pancreatic Peptide
What are the main hormone products of the Kidney
Erythropoietin
Calcitrol
Renin
What are the main hormone products of the GI Tract
Gastrin
Secretin
Cholecystokinin (CCK)
Gastric Inhibitory Peptide (GIP)
Glucagon-Like Peptides (GLPs)
Motilin
Ghrelin
What are the main hormone products of the Testis
Testosterone
What are the main hormone products of the Ovaries
Estrogen
Progesterone
What are the main hormone products of the Adipose Tissue
Leptin
Adiponectin
Resistin
What are the main hormone products of the Anterior Pituitary
Growth Hormone (GH)
Adrenocorticotropic Hormone (ACTH)
Follicle-Stimulating Hormone (FSH)
Leutinizing Hormone (LH)
Prolactin (PRL)
Thyroid Stimulating Hormone (TSH)
What are the main hormone products of the Posterior Pituitary
Antidiuretic Hormone (ADH)
Oxytocin (OT)
What are the main hormone products of the Hypothalamus
Thyroid Releasing Hormone (TRH)
Growth Hormone Releasing Hormone (GHRH)
Growth Hormone Inhibiting Hormone (GHIH)
Somatostatin (SS)
Gonadotropin Releasing Hormone (GnRH)
Prolactin Releasing Hormone (PRH)
Prolactin Inhibiting Hormone (PIH or Dopamine)
Corticotropin Releasing Hormone (CRH)
What is the function of the endocrine systrem?
Regulates growth, development, metabolism, and reproduction through a network of hormones and receptors utilizing endocrine, paracrine, autocrine, neurocrine, and transcriptional signaling mechanisms throughout the body
What does excess secretion of growth hormone (GH) during development lead to?
Gigantism - greatly accelerated rate of growth with delayed closure of the epiphyses
What does excess secretion of growth hormone (GH) in adulthood lead to?
Acromegaly - causes slow, progressive changes including coarsening of the facial features, protrusion of the lower jaw, and enlargement of the hands and feet
Tell me about the hypothalamus
Part of the diencephalon
Contains nuclei - including the supraoptic nucleus (SON), para-ventricular nucleus (PVN), and arcuate nucleus (AN)
Synthesizes neuro-hormones (releasing and inhibiting hormones), which bind to membrane receptors on target cells in the anterior pituitary (AP)
What are the releasing and inhibiting hormones of the hypothalamus?
Thyroid Releasing Hormone (TRH)
Gonadotropin Releasing Hormone (GnRH)
Growth Hormone Releasing Hormone (GHRH)
Growth Hormone Inhibiting Hormone (GHIH) or Somatostatin
Prolactin Releasing Factor (PRF)
Prolactin Inhibiting Hormone (PIF) or Dopamine (DA)
Corticotropin Releasing Hormone (CRH)
What is Pulsatile Secretion?
Hormones made by the hypothalamus, pituitary, and some of the other endocrine glands are released in short pulses or bursts
When used in treatment of disease, they must be administered in a way that mimics the endogenous pattern of release in order to be effective
Tell me about the pituitary gland
AKA hypophysis
Has two main lobes: anterior lobe (adenohypophysis) and posterior lobe (neurohypophysis or pars nervosa)
Tell me about the Anterior Pituitary
Mainly the pars distalis, consists of glandular epithelium originating from Rathke’s pouch (an invagination of ectoderm in the oropharynx) with hormone-secreting cells arranged in cords/clusters
Sella Turcica - part of sphenoid bone where pituitary gland sits which limits pituitary expansion - therefore if pituitary enlarges, it puts pressure on adjacent structures (optic chiasm)
What are the hormones released from the Anterior Pituitary
Thyroid Stimulating Hormone (TSH)
Leutinizing Hormone (LH)
Follicle Stimulating Hormone (FSH)
Growth Hormone (GH)
Prolactin (PRL)
Adrenocorticotropic Hormone (ACTH)
What is the Hypothalamic-Hypophyseal Portal System (HHPS)
A neurovascular link to the endocrine system
Provides a direct route for hypothalamic hormones to reach the AP - consists of 2 capillary beds (plexuses) connected by long portal veins
i) primary plexus is located in the median eminence; ii) secondary plexus opens up onto its target cells in the anterior pituitary
Purpose: deliver hypothalamic hormones quickly and at very high concentrations
Vessels in HHPS are fennestrated, so substances that would normally be excluded by the blood brain barrier are allowed to pass freely and in both directions
Hypothalamus (Releasing/Inhibiting Hormones) -> Primary plexus (Median Eminence) -> Long Portal Veins -> Secondary Plexus -> -> -> Target cells in the AP
Tell me about the Posterior Pituitary
Pars nervosa or neurohypophysis
Derives from neuroectoderm
Not a true endocrine gland
Consists of glial cells (or pituicytes) and axon terminals extending from the hypothalamus
Doesn’t synthesize hormones of its own, but stores hormones synthesized in the hypothalamus
Posterior Pituitary Hormones
Vasopressin (VP) or Antidiuretic Hormone (ADH)
Oxytocin (OT)
*Made in the SON and PVN of the hypothalamus and then delivered to the PP by axonal transport, where they are stored
What is the Hypothalamic-Hypophyseal Tract
Long axons pass from the hypothalamus and ME through a hypothalamic-hypophyseal tract in the infundibular stalk to the PP
Action Potentials’ carried over this tract have the capacity to trigger the release of hormones from vesicles in the PP
Once released, they can gain access to the bloodstream in order to reach their target cells in the periphery
Pituitary Gland Histology
Anterior appears darker due to cells that are basophilic in nature
Herring bodies - histologically detectable aggregates that form when hormones accumulate in the posterior pituitary
Somatotropes -> GH = acidophilic
Lactotropes -> PRL = acidophilic
Thyrotropes -> TSH = basophilic
Corticotropes -> ACTH = basophilic
Gonadotropes -> Gonadotropins: LH, FSH = basophilic
Chromophils = acidophils (stain pink; secrete GH, PRL) and basophiles (stain blue; secrete TSH, ACTH, LH, FSH)
Tell me about the Adrenal Glands
Vital to life
Each adrenal gland has a cortex, originating from mesoderm
A medulla, originating from ectoderm
vital in organisms response to environmental stress
Produce steroids and catecholamines that participate in the sympathetic nervous system (SNS) to bring about the fight or flight response = essential for self-preservation
Also involved in metabolism, fluid homeostasis, blood pressure, vasomotor tone, heart rate, cardiac output, and other processes throughout the body
Clinically, catecholamines are used to counteract cardiac arrest, treat shock, and dilate the bronchioles in asthmatics; Glucocorticoids, like cortisol, are also used in these and other conditions, mainly for their ability to reduce inflammatory- and autoimmune reactions
Adrenal Gland Hormones
Adrenal Cortex:
Mineralocorticoids = aldosterone from zona glomerulosa
Glucocorticoids = cortisol from zona fasiculata
Adrenal androgens = DHEA, Androstenedione from zona reticularis
Adrenal Medulla:
Catecholamine = Norepinephrine from Chromaffin cells
Catecholamine = Epinephrine from Chromaffine cells
Adrenal Cortex
Divided into 3 histologic zones:
Zona glomerulosa
Zona fasiculata
Zona reticularis
Adrenal Medulla
Located at the center of the adrenal gland, surrounded by the cortex
Unlike cortex, originates from ectoderm and cells are Chromaffin cells
Chromaffin cells - considered to be modified postganglionic sympathetic neurons and don’t have axons, dendrites, and don’t make synapses; during development, cortisol promotes differentiation of chromaffin cells and inhibits formation of neuronal processes (axons, dendrites)
Explanation of Adrenal Glands
After catecholamines are synthesized, they’re stored in granules within chromaffin cells for fast release in response to stressful stimuli
When these stimuli activate the SNS, action potentials travel through preganglionic sympathetic neurons entering the adrenal medulla and trigger the release of acetylcholine, ACh, which acts as a neurotransmitter
Instead of acting at a synapse, ACh acts at a nerve-gland junction by binding to nicotinic receptors on chromaffin cell membranes initiating the release of catecholamines from pre-formed granules into the bloodstream
Tell me about Parathyroid Glands
Embedded in the connective of the thyroid
Contain principal cells (chief cells) and oxyphil cells
Principal cells secrete PTH, which participates in blood calcium regulation
Tell me about the Thyroid Gland
Contains follicle cells that synthesize T3 and T3 as well as parafollicular “C” cells, which secrete calcitonin (CT)
Thyroid hormone synthesis is triggered by TSH from the anterior pituitary
TSH levels controlled both by the positive effects of TRH (From the hypothalamus) and by the negative effects of elevated serum levels of T3-T4 via negative feedback
TSH and T3-T4 are reciprocally related
Interplay between hormones in the HPT axis is what keeps T3 and T4 within the normal, euthyroid range
Hypothalamic-Pituitary-Thyroid Gland (HPT) Axis
When thyroid hormone levels are too high in the blood, they exert a negative feedback over the AP and hypothalamus to prevent further production of TSH and TRH, respectively
When circulating levels of T3-T4 become too low, the inhibitory effects over TRH and TSH are removed, and thyroid hormone levels return to normal
When TRH is released from the hypothalamus it binds to receptors on AP thyrotropes to trigger the release of TSH
TSH causes the size, number, and activity of thyroid follicle cells to increase and it stimulates every step in the pathway of thyroid hormone synthesis
Thyroid hormones travel through the entire circulation, diffuse into target cells, and bind to nuclear receptors in order to activate target gene transcription
Thyroid binding globulin (TBG) is the main transport protein for thyroid hormones traveling through the bloodstream
Thyroid Follicle Histology
Thyroid follicle is the structural and functional unit of the thyroid gland; thyroid gland contains hundred of ‘thyroid follicles’
Each thyroid follicle consists of a single layer of cuboidal epithelial cells, aka ‘follicle’ cells’ - the cells that produce thyroid hormones and release them into the bloodstream
Follicle cells have 2 functional surfaces: apical and basal; apical side faces the lumen which stores colloid; basal side faces the bloodstream
Main constituent of colloid is “thyroglobulin” (TG); an iodinated glycoprotein that is endocytosed into the follicle cell for cleaved into thyroid hormones and release into the bloodstream
Para-follicular cells, which produce CT, are located between follicles
HPT Axis Regulation
Defects at any level can lead to increases or decreases in thyroid hormone production (hyper- or hypothyroidism)
Most common cause of thyroid dysfunction originates in the thyroid gland itself = PRIMARY
Secondary dysfunction is used when a problem, originating in the AP, causes thyroid hormone levels to become abnormal; SECONDARY = Anterior Pituitary
Central or Tertiary describe the impact of problems in the hypothalamus or higher brain centers on the thyroid; CENTRAL (TERTIARY) = hypothalamus
Peripheral hypothyroidism = target tissues have become insensitive to the effects of thyroid hormones; results from mutations in the genes encoding thyroid hormone
Hypothalamic-Pituitary-Target Organ Axis
Feedback signaling: hormones released by the hypothalamus stimulate the pituitary gland hormones that have the capacity to regulate downstream target organs; if hormone secreted by a target organ increases beyond a certain critical upper leve, it exerts feedback inhibition over the anterior pituitary and hypothalamus to prevent continued stimulation for its release
Hormone = Thyroid hormones: T3-T4
Origin = follicle cells in the thyroid gland
Positive Regulator = TSH from the anterior pituitary
Negative Regulator = Feedback inhibition of TRH from the hypothalamus and TSH from the AP, exerted by high levels of T3-T4 in circulation
Targets = thyroid hormones increase oxygen consumption and metabolic rate in nearly every cell in the body
Hypothalamic-Pituitary-Adrenal Gland Axis
Hypothalamus –CRH–>Antr Pituitary – ACTH –> Adrenal Cortex –> decreased Cortisol
Decreased cortisol -> + Hypothalamus and + Antr Pituitary
Hypothalamus –| CRH –> Antr Pituitary –| ACTH –> increased Cortisol
Increased cortisol -> - Hypothalamus and - Antr Pituitary
Central = Hypothalamus
Secondary = Anterior pituitary
Primary = Adrenal cortex
In primary hypocortisolism, cortisol is high and ACTH is low. Where is the problem?
Problem with the Adrenal Cortex.
Adrenal cortex is able to make cortisol freely
Negative effects still happening onto Antr Pituitary so ACTH is still low
Hypothalamic-Pituitary-Thyroid Gland Axis
When TRH is released from the hypothalamus, it binds to receptors on AP thyrotropes to trigger release of TSH
TSH binds to receptors on follicle cell membranes in the thyroid gland to upregulate the synthesis of T3 and T4
Thyroid hormones travel through the entire circulation, diffuse into target cells, and bind to intracellular receptors
Thyroid hormone-receptor complexes will ultimately exert actiosn by up-regulating expression of target genes
In an individual with hypothyroidism due to low T3-T4 levels, how would you expect TSH levels to change and why?
Low T3-T4 levels will increase levels of TSH in a normal individual; the thyroid is not responsive to TSH
If the low thyroid hormone levels are caused by destruction of the thyroid gland (follicles), which of the following terms would you use to describe the patient’s hypothyroidism?
Primary
A 37yo woman comes to your office with complaints that suggest she may have hypothyroidism. These complaints include fatigue; dry, flaky skin; difficulty concentrating; and feelign cold when everyone else is too warm. Elevated levels of what hormone would best support a diagnosis of hypothyroidism?
TSH
List four hormones in the HPT axis
T3
T4
TRH
TSH
In an individual with low T3-T4 levels, how would you expect TSH levels to change?
TSH levels will increase
What hormones in the HPT axis have the most obvious reciprocal activity? What is the clinical significance of this?
TSH and T3-T4
In hypothyroidism: low T3-T4 and high TSH
In hyperthyroidism: high T3-T4 and low TSH
If the levels of T4 and TSH in circulation are both below normal, where is the problem most likely to have originated?
Anterior pituitary - secondary
If the circulating levels of T4 are low or normal, but TSH levels are elevated, where is the problem likely to have originated?
Thyroid gland