Download 1 Chapter 2: The Endocrine System Chemical Communication

1
Chapter 2: The Endocrine System
Chemical Communication






Information is communicated by release of chemicals and detection by receptors
Intracrine – chemical mediation of intracellular events (hormones and pheromones)
Autocrine cells - secrete products that may affect processes of cells which produce them (i.e.
steroid producing cells that have receptors for those steroids)
Paracrine agents – chemicals which are released by one cell and impact neighboring cells (i.e.
neurons)
Ectocrine substances – released outside individual and impact other animals (i.e. pheromones)
Endocrine cells – produce chemicals that travel via the bloodstream to distant cells
General Features of the Endocrine System





Endocrinology – study of endocrine glands and associated hormones
Neurohormone – special hormone released by neuron into blood
Neuroendocrinology – study of transduction of neural to hormonal signal and other
relationships between nervous and endocrine system
 General features of endocrine system:
o Glands are ductless
o Glands have rich blood supply
o Hormones produced by glands are secreted into the blood
o Hormones can travel to any cell and interact with all cells that have appropriate
receptors
o Receptors are specific binding sites embedded in cell membrane that interact with a
particular hormone
 Exocrine glands – have ducts/tubes into which products are release (i.e. salivary and sweat
glands)
o Some glands have endo- and exocrine functions – pancreas
exocytosis – extrusion of hormones stored in vesicles of endocrine cells (only water soluble
hormones)
o Steroids and lipid soluble hormones are not stored in vesicles but secreted as soon as
synthesized and form a reversible bond with a carrier protein
Removal of hormones is by uptake and degradation (metabolism) by kidney and liver
The Endocrine Glands

There are 4 classes of hormones:
o Peptides/proteins
o Steroids
o Monoamines
o Lipi-based
2








Generally only one class is produced by one endocrine gland
Hypothalamus – located beneath thalamus at base of the brain
Pituitary – located at the base of the skull in sella tursica and attached to hypothalamus near
median eminence by the infundibulum (also known as the pituitary stalk
Thyroid gland – located in upper trachea
Pancreas – in curve of duodenum (small intestine) behind stomach and liver
Adrenal glands – bilateral organs on top of kidneys
Pineal gland – aka epiphysis located between telencephalon and diencephalon
Gonads – reproductive organs – 2 types
o Testes – in a sac outside abdomen called the scrotum in male
o Ovaries – in abdomen of female, a temporary endocrine organ forms during pregnancy
(placenta )
Hypothalamus



Primary interface of endocrine and nervous system
A collection of neuronal cell bodies (nuclei) at the base of the brain which receives projections from
higher brain sites
Neurosecretory cells – in hypothalamus, function as endocrine glands but are neurons and
therefore produce neurohormones which are released into blood vessels in the anterior pituitary
Pituitary Gland



Really two distinct glands fused into one
Anterior pituitary – derived from upper palate and connected to posterior via the pars intermedia
o Receives neurohormones from hypothalamus via the hypothalamic hypophyseal portal system
down the infundibulum ( direction of blood flow is primarily from hypothalamus to pituitary)
o These are releasing hormones which stimulate/inhibit release of anterior pituitary hormones
o Tropic – anterior pituitary hormones which stimulate physiological processes by directly acting
on target tissues or by causing endocrine glands to release hormones
o Contains 3 types of cells which each produce a distinct type of tropic hormone
Posterior pituitary – derived from the base of the brain
o Receives neurohormones from hypothalamus which are directly secreted into the blood
o Really only acts as a reservoir for two neurohormones – oxytocin and vasopressin – by holding
them in vesicles which can be released in response to neural impulse
Thyroid Gland



Has many follicles (sphere shaped colloid filled structures) which produce thyroid hormone in
response to anterior pituitary topic hormones
It stores large quantities of the thyroid hormone (up to 90 days worth) b/c it is produce from iodine
which is often scarce in human diet
C-cells – produce calcitonin (involved in calcium metabolism)
3

Parathyroid gland – has 2 lobes, which secrete parathyroid hormone important in calcium
regulation
Pancreas



Has both endo- and exocrine function
Exocrine function – produce and secrete digestive “juices” to intestines making up the majority of
the pancreas
Endocrine function – islet of langerhans – have 4 cell types (α, β, δ, and polypeptide secreting cells)
o Each cell types secretes a different hormone (β cells secreteinsulin)
o Islets of langerhans innervated by vagus nerve which can respond to glucose concentrations,
anticipate arrival of food to stomach, etc.
Gastrointestinal Tract



Endocrine cells scattered throughout in what is considered a primitive organization
Ghrelin – recently discovered hormone to be produced in the stomach
3 major gastrointestinal hormones – gastrin, secretin, cholesystokinin – which control digestion
Adrenal Glands



There are two and they are actually composed of 2 distinct organs (cortex and medulla)
Adrenal Medulla –
o Make up the inner part of adrenal glands made of chromaffin cells (named because they have a
high affinity for colored stains)
o Functions as part of the Autonomic Nervous System
o Releases three monoamine hormones: epinephrine, norepinephrine, dopamine
o Also releases enkephalins (protein hormones)
Adrenal Cortex –
o outer part of adrenal glands, composed of 3 zones:
 zona glomerulosa – composes 10-15% of cortex and is characterized by whorls of
epithelial cells
 zona fasciculate – composes 75-80% of cortex and is arranged in bands of epithelial cells
 zona reticularis - composes 5-15% of cortex disorderly arranged
o Human fetuses have a 4th layer known as the fetal zone which composes the majority of the
cortex (X zone is equivalent in nonhuman animals)
o Each layer produces different hormones (all of which are steroids though) and has a different
regulation mechanism
The Pineal Gland

Strange evolutionary history –
o In mammals, the pineal cells (pinealocytes) function as secretory structures
4
o

In nonavian and nonmammal animals, it functions as a photoreceptor organ (often called third
eye)
Secretes melatonin from serotonin
The Gonads




Have two functions: production of gametes and production of hormones (primarily steroids for
development of gametes and secondary sex characteristics)
Regulated by gonadotropins (tropin hormones from anterior pituitary)
The Testes –
o Bilateral organs located in external sac (scrotum)
o Seminiferous tubules – long tubes in which sperm undergo stages of maturation
(spermatogenesis)
o Sertoli cells – located along base of seminiferous tubules where the heads of developing sperm
are embedded
 Provide nourishment to developing sperm and produce inhibin (peptide hormone
regulating gonadotropins)
o Leydig cells – interspersed among tubules and produce androgens
The Ovaries –
o Bilateral organs located beneath kidneys
o Have cyclic changes in production of gametes and production of hormones (as opposed to
testes which are tonic or constant in their function)
o Follicles –contain developing egg (ovum)
o Corpora lutea – structures that develop from follicles after the ovum is released
o Stroma – supporting tissue of the ovaries, consists of connective tissue and interstitial cells
o Ovaries contain approximately half a million undeveloped follicles and so no additional gametes
are produce during lifetime
o Degeneration of follicles over time is known as atresia
o Granulosa cell - surround oocyte of collicle and produce inhibin and activin which suppress and
enhance (respectively) hormone secretin in hypothalamus and pituitary
o Theca interna and theca externa cells – surround granulose cells and secrete estrogens
o Zona pellucida – cells surrounding cell membrane of maturing ovum ( when this occurs, it is
called a secondary follicle)
o after zona pellucida forms, a space between the epithelial cells and ovum develops (called
antrum) and it is filled with fluid prior to ovulation
 as the antrum grows in size, it is called a tertiary follicle
o Prior to ovulation, ovum is maximal size and is called a Graafian follicle
 Ovulation – eruption of graafian follicle and ovum travels to the mouth of the oviduct
through which it can be transported to uterus
o Granulosa cells of erupted follicle and surrounding thecal cells forms the corpus luteum which
persists for several days producing progestins, it eventually degenerates leaving a scar known
as the white body which does not produce hormones
5
o

Follicular Phase:
 The theca interna develops receptors for luteininzing hormone (LH) from anterior pituitary
 production of androgens
 The granulose cells develop receptors for follicle-stimulating hormone (FSH)  convert
androgens into estrogens
The Placenta
o Temporary endocrine organ developing during pregnancy
o Maintains nutritional, respiratory, and excretory functions for fetus
o Source of steroid and peptide hormones that affect mother and fetus
 Including human chorionic gonadotropin – which can be measured as the form of a
pregnancy test
Cellular and Molecular Mechanisms of Hormone Action

Signal transduction – hormone message transformed into intracellular events that ultimately affect
cell function
o The sequence of events from the time a hormone binds to its receptor to the ultimate response
of the target cell
Hormone Receptor Types


Steroid Receptors – located inside cells (in cytosol or nucleus), when receptors bind to hormone
they move into nucleus to regulate gene transcription
Protein and Peptide Hormone Receptors - embedded in the cell membrane containing 3 domains:
o Extracellular domain which binds to ligand (hormone)
o Transmembrane domain
o Cytoplasmic domain
o These receptors are dynamic and they turn over rapidly
o Enzyme amplification – a single protein/peptide hormone molecule can trigger synthesis of
thousands of enzyme molecules
o Can be divided into two classes:
 Intrinsic enzymatic activity – these receptors have a tyrosine kinase which phosphorylate
and thereby activate other intracellular proteins
 Require second messenger to exert effects – second messenger is a G-protein which can
bind and hydrolyze GTP
 There are several difference kinds of G-proteins by they all have α, β, γ subunits
 G-proteins activate an intracellular enzyme (adenylate cyclise) which stimulates the
formation of cyclic adenosine monophosphate (cAMP)
 cAMP then activates a specific protein kinase in the cell
 G-proteins can also open ion channels, letting calcium into cell, which eventually
stimulates cAMP production which then activates specific kinases
 G-coupled protein receptors have 7 transmembrane domains –
 For glucagon, oxytocin, and vasopressin receptors
6

There are many signal transduction pathways involving G-proteins, they can either
increase or decrease cAMP activity as well as acting without the help of cAMP or cGMP
Transcription, Translation, and Post-Transcriptional Events





Transcription factors – compounds that bind to DNA sequence where gene to be transcribed is
located and facilitates transcription of the gene
A gene may be divided into parts because introns are located inside the gene which are non-coding
– but they are removed before entering cytosol as mRNA
Preprohormone – the first product of translation of mRNA by a ribosome
Prohormone – product after the signal sequence at the N-terminal of the preprohormone is
removed
The prohormone usually has additional post-translation processing within the rough endoplasmic
reticulum, the golgi apparatus and the vesicle in which is it stored before it is the final product
The Major Vertebrate Hormones

4 classes of hormones exist: proteins and peptides, steroids, monoamines, and lipid based
Protein and Peptide Hormones




They are most common in vertebrates; made of amino acids
Peptide hormones – only a few amino acids long
Protein/polypeptide hormones – longer strands of amino acids
They are stored in endocrine cells and released by exocytosis; they are blood soluble; removed from
body via degradation or excretion
 Biological half-life – the amount of time to remove half of a hormone in the blood
o Generally, larger proteins have longer half-life than shorter ones
 Hypothalamic Hormones –
o Usually small and act as releasing or inhibiting hormones
o Releasing hormones – thyrotropin-releasing hormone (TRH), somatocrinin (growth hormonereleasing hormone [GHRH]), gonadotropin-releasing hormone (GnRH), melanotropin-releasing
hormone (MRH) abd corticotrophin-releasing hormone (CRH)
o inhibiting hormone – growth hormone-inhibiting hormone (somatostatin)
o Dopamine, usually considered a neurotransmitter, acts to inhibit prolactin and melanotropin
from the anterior pituitary – referred to as prolactin inhibitory hormone (PIH) and melanotropin
inhibitory hormone (MIH)
o Hypocretin – (aka orexin ) is also found in hypothalamus and is involved in sleep, metabolic
balance, and activation of the sympathetic nervous system
 Anterior Pituitary Hormone
o 15-220 amino acids long
o Glycoproteins - hormones which have a primary make-up of carbohydrates
7
o
Gonadotropins – hormones which stimulate steroidogenesis in the gonads as well as
development and maturation of gametes
o Hormones secrete by basophil cells:
 Luteinizing hormone (LH) – a glycoprotein and gonadotropin, promotes formation of
corpora lutea in females and testosterone production in males
 Follicle Stimulating Hormone (FSH) – a glycoprotein and gonadotropin, stimulates follicle
development in females and sperm production in males
 Thyroid-Stimulating Hormone (TSH) – glycoprotein, stimulates thyroid hormone secretion
o Hormones secreted by acidophils:
 Growth hormone (GH) – secreted in response to GHRH from hypothalamus; stimulates
somatic/body growth by stimulating production of growth-regulating substances
(somatomedins) from the liver, kidneys and other tissues; has an inherent prolactn activity
 Prolactin – release stimulating by TRH from hypothalamus; promotes lactationin females,
formation of corpora lutea, and has osmoregulatory effects
o Hormones secreted by chromatophobes:
 Adrenocorticotropic hormone (ACTH) – released in response to CRH from hypothalamus
and stimulates the adrenal cortex to secrete corticoids; has inherent MSH activity (which
stimulates melanocytes to create pigmentation)
 Produced from parent molecule pro-opiomelanocortin (POMC) by cleavage
o Other products of POMC include β-endorphins, met-enkephalin, and
melanocyte-stimulating hormone (MSH)
 Posterior Pituitary Hormones
o Produces two nonapeptides – produced from prohormones that also include carrier protein
neurophysin (which increases the half life of the nonapeptides)
o Oxytocin – a nonapeptide, influences reproductive function in mammals by causing uterine
contractions in labor; also important in the sucking reflex allowing a females milk to be let down
so the baby can feed)
o Vasopressin – (aka antidiuretic hormone [ADH]) a nonapeptide, acts to retain water in
vertebrates and regulates blood pressure by inducing constriction of the blood vessels
 Thyroid Hormones
o All hormones are derived from tyrosine, so they are not really peptides but monoamines
o Thyroxine (T4) – most common thyroid hormone, produced from iodine
o Triiodothyronine (T3) – also produced from iodine
o Both of these increase oxidation rates in tissue, regulate metabolic actions, can release heat
through metabolism of glucose (allow for adaptation in changing temperatures), affect
reproduction, and are important in growth and differentiation
o Hypothyroidism can have many detrimental effects including mental retardation (cretinism)
 Parathyroid and C-Cell Hormones
o Both produce proteins and are involved in calcium metabolism
o Parathyroid Hormone (PTH) – elevates calcium blood levels by increasing resorption of calcium
from the bone and absorption of calcium from gut
8
o
Calcitonin (CT) – acts in opposition to PTH and lowers blood levels of calcium by inhibiting
release of calcium from bone
 Gastrointestinal Hormones
o Supplement action of the autonomic nervous system mediating the process of digestion
o Secretin - secreted from duodenum; stimulates acinar cells of pancreas to produce water and
bicarbonate (which aid in digestion); it stimulates hepatic bile flow from liver, pepsin secretion,
and insulin secretion
o GAstrin – produced by g-cells in the antral glands of the stomach; release is promoted by
acetylcholine