The endocrine system Flashcards
Nervous system function
Produces short-term but very specific responses to environmental stimuli
Endocrine gland cells
Release chemicals into the bloodstream for distribution throughout the body that mostly work over the medium to long term to achieve homeostatic regulations
Autocrine signals
act on the same cells that produce the hormones
Paracrine signals
act on cells nearby to where the hormone is produced
Receptors required for hormones to signal
Receptor on cell membrane, receptor in cytosol and receptor in nucleus
Endocrine signals
act on cells that can be anywhere in the body i.e long distance signals
Types of hormones
Amino acid derivatives
Peptide hormones
Steroid hormones
Endocrine system function
Responsible for co-ordinating the homeostatic regulation of fluid and electrolyte balance, cell and tissue metabolism, growth and development, and reproductive functions.
Hormone function
Alter the activities of many different tissues and organs simultaneously and the ability of a tissue to respond is dictated by the presence or absence of the receptor for a hormone being expressed in a cell.
Amino acid derivatives examples
Thyroid hormone, catecholamines, melatonin, serotonin
Amino acid derivative hormones
- A range of different enzymes are responsible for making these from their amino acid precursor.
- Usually produced in an endocrine tissue and act on different cells that possess a receptor for it on it’s cell
surface. - Once transported into cells they are broken down so signal stops.
Peptide hormones
(e.g all pituitary hormones plus
hormones in Islets of Langerhans).
These peptides are directly encoded for by genes but also often require additional enzymes to cleave and process them into their final active form. Biggest form of hormones so can’t get into cells so act via receptors at the plasma membrane.
These are usually made as a non-functional prohormone but the endocrine cells contain specialist proteases that can cleave these into their final processed form.
Proglucagon gene
Codes for several hormones via transcription and translation which results in proglucagon peptide.
This is not active but contains coding sequence for glucagon, coding sequence for GLP-1 and coding sequence for GLP-2.
Cleavage of GLP-1 From Proglucagon in Intestinal L-Cells
GLP-1 is Cleaved by Prohormone Convertase-1 (PC1) in L-cells and released to blood to become active.
Active GLP-1 is rapidly cleaved by DPP-IV (Half life of active GLP-1
Is only a few minutes) to become inactive
Steroid hormones
Released from reproductive organs
and adrenals. Synthesized from cholesterol so usually lipophilic and can cross directly into cells. Usually bind to receptors that locate to nucleus and regulate gene
expression.
Synthesis of steroid hormones
Cholesterol is modified by enzymes to make steroid hormones such as aldosterone and cortisol in the adrenal medulla and estradiol in the ovary
5 main factors of the endocrine system that are regulated to achieve homeostatic balance
- The rate of production of the active form of the hormone.
- The rate of release of the hormone from the endocrine tissue.
- Whether the hormone is sequestered by binding proteins in the circulation.
- The rate of breakdown of the hormones
- The location and levels of receptors for the hormone in specific
tissues.
Why do endocrine disorders develop
- Arise due to abnormalities in the endocrine gland
- Arise due to abnormalities in the endocrine or neural regulatory mechanisms.
- Arise due to abnormalities in the target tissue.
Endocrine reflexes are triggered by
- Humoral stimuli (changes in the composition of the extracellular fluid and in the circulation)
- Hormonal stimuli (arrival or removal of a specific hormone)
- Neural stimuli (the arrival of neurotransmitters at neuro-
glandular junctions)
Explain direct negative feedback of endocrine activity
a. The endocrine cell responds to a disturbance in homeostasis by releasing its hormone into the circulatory system.
b. The released hormone stimulates a target cell.
c. The target cell response restores homeostasis and eliminates the source of stimulation of the endocrine cell.
Pineal gland
~ The small, red, pine cone-shaped pineal gland, or epiphysis cerebri, is part of the epithalamus.
~ The pineal gland contains neurons, glial cells, and special secretory cells called pinealocytes.
~ Pinealocytes synthesise the hormone melatonin, which is derived from molecules of the neurotransmitter serotonin.
Melatonin function
~Slows the maturation of sperm, oocytes, and reproductive organs by inhibiting the production of a hypothalamic releasing factor that stimulates FSH and LH secretion. Melatonin has many other important biological actions, especially well known in regards to sleep.
~ Axon collaterals from the visual pathways enter the pineal gland and affect the rate of melatonin production- entrainment by light (stimulated by dark). However, circadian rhythms also play an important role.
~ This cycle is apparently important in regulating circadian rhythms, our natural awake-asleep cycles. Levels are highest at night (opposite of cortisol).
The hypothalamus
An area of brain responsible for coordinating a range of neural, endocrine and humoral signals. For example it regulates metabolism after receiving signals from leptin produced in fat tissue. Closely linked to the pituitary gland.
Hypothalamus hormones
Produces a range of hormones that stimulate the release of other hormones in the pituitary e.g CRH (Corticotrophin
Releasing Hormone), TrH (Thyrotropin releasing Hormone) and GHRH (Growth Hormone Releasing Hormone)
Produces two hormones that have direct functional effects- ADH (Anti-diuretic hormone also called Vasopressin) and Oxytocin. Sends signal via complex set of neuronal signals e.g. to the adrenal medulla to control adrenaline and noradrenaline release.
Pars distalis of anterior lobe of pituitary
Secretes other pituitary hormones
Pars intermedia
Secretes MSH
Pars nervosa of posterior lobe
Releases ADH and oxytocin
Posterior lobe of pituitary
~ The posterior lobe of the pituitary gland is also called the neurohypophysis or pars nervosa.
~ The hypothalamic neurons manufacture ADH (supraoptic nuclei) and oxytocin (paraventricular nuclei)
~ ADH and oxytocin are called neurosecretions because they are produced and released by neurons
ADH
- Released in response to a variety of stimuli, most notably to a rise in the concentration of electrolytes in the blood or a fall in blood volume or pressure.
- the primary function of ADH is to decrease the amount of water lost at the kidneys
- ADH also causes the constriction of peripheral blood vessels, which helps to elevate blood pressure.
Oxytocin in females and males
- The functions of oxytocin are best known in women, where it stimulates the contractions of smooth muscle cells in the uterus and contractile (myoepithelial) cells surrounding the secretory cells of the mammary glands.
- in the human male, oxytocin causes smooth muscle contractions in the prostate gland
Thymus
~ The thymus produces several hormones important to the development and maintenance of normal immunological
defenses.
~ Thymosin was the name originally given to a thymic extract that promoted the development and maturation of lymphocytes
and thus increased the effectiveness of the immune system.
~ Thymosin is a blend of several different, complementary hormones (thymosin-1, thymopoietin, thymopentin, thymulin,
thymic humoral factor, and IGF-1).
Thyroid hormones
Two thyroid hormones -thyroxine (T4), and
triiodothyronine (T3)
Thyroid Hormone Synthesis in Thyroid Follicles
- Follicular cell synthesizes enzymes and thyroglobulin for colloid
- I- (iodine) is co-transported into the cell with Na+ and transported into colloid
- Enzymes add iodine to thyroglobulin to make T3 and T4.
- Thyroglobulin is taken back into the cell
- Intracellular enzymes separate T3 and T4 from the protein
- Free T3 and T4 enter the circulation
How is thyroid hormone secretion regulated?
Homeostasis Disturbed: Low T3/T4 or body temperature.
Hypothalamus Response: Releases TRH.
Pituitary Gland Response: TRH stimulates the pituitary to release TSH.
Thyroid Gland Activation: TSH stimulates the thyroid to release T3/T4.
Homeostasis Restored: Increased T3/T4 levels restore balance.
Negative Feedback: Normal T3/T4 levels inhibit TRH and TSH release.
This feedback loop maintains metabolic balance and body temperature.
Calcitonin actions
~ Calcitonin lowers calcium ion concentrations by:
1. Inhibiting osteoclasts
2. Stimulating calcium ion excretion at the kidneys
~ The actions of calcitonin are opposed by those of
parathyroid hormone, produced by the parathyroid
glands.
Parathyroid gland
~Like the C cells of the thyroid, the chief cells of the
parathyroids monitor the circulating concentration of calcium ions.
~ When calcium levels fall, production and release of
parathyroid hormone (PTH) is triggered.
~ PTH stimulates osteoclasts to raise calcium levels and also regulates activation of Vitamin-D
~ PTH also reduces urinary excretion of calcium ions.
~ PTH stimulates the production of calcitriol, a kidney hormone that promotes intestinal absorption of calcium.
The Adrenal Cortex: Zona Glomerulosa
~ The zona glomerulosa of the adrenal cortex produces
mineralocorticoids (MC), steroid hormones that affect the electrolyte composition of body fluids.
~ Aldosterone is the principal mineralocorticoid and it has two main functions. Targets kidney cells that regulate the ionic composition of the
urine by causing:
- the retention of sodium ions and water, thereby reducing fluid losses in the urine.
- the loss of potassium ions in the urine and at other sites as well.
~ Aldosterone also reduces sodium and water losses at the sweat glands and salivary glands and along the digestive tract.
Release of Aldosterone
~ Aldosterone secretion also occurs when the zona glomerulosa is stimulated by any one of three events:
- A fall in blood sodium levels
- A rise in blood potassium levels
- Arrival of the hormone angiotensin II
Adrenal Cortex: Zona Fasciculata
~ ACTH from the anterior lobe of the pituitary gland, stimulates
steroid production in the zona fasciculata of the adrenal cortex
~ This zone produces steroid hormones collectively known as glucocorticoids (GC) because of their effects on glucose metabolism.
~ Cortisol and corticosterone are the most important
glucocorticoids secreted by the adrenal cortex; the liver converts some of the circulating cortisol to cortisone, another active
glucocorticoid.
~ These hormones have a wide range of effects including speed up the rates of glucose synthesis and glycogen formation,
especially within the liver and also down regulate immune system
Glucocorticoids
*Cortisol and corticosterone are the most important
glucocorticoids secreted by the adrenal cortex; the liver
converts some of the circulating cortisol to cortisone, another active glucocorticoid.
- These hormones have a wide range of effects as receptors for glucocorticoids are in most cells.
- These hormones have long term developmental roles but over shorter term they have two important effects
Glucocorticoids - increase availability of nutrients for brain and heart by increasing rates of glucose synthesis and glycogen formation through liver and stopping uptake of nutrients into other peripheral tissues.
- suppressing immune system by reducing numbers of leukocytes.
Adrenal Cortex: Zona Reticularis
The zona reticularis normally secretes small amounts of sex hormones called androgens.
~ Adrenal androgens stimulate the development of pubic hair in boys and girls before puberty.
~ Adrenal androgens are not important in adult men, whose testes produce androgens in relatively large amounts.
~ In adult women adrenal androgens promote muscle
mass, stimulate blood cell formation, and support the
libido.
Adrenal Medulla
~ Pheochromocytes, or chromaffin cells produce catecholamines adrenaline (also known as epinephrine) and noradrenaline (also known as norepinephrine). These are large, rounded cells of the medulla that resemble the neurons in sympathetic ganglia. These cells are innervated by preganglionic sympathetic fibers; sympathetic activation, provided by the splanchnic nerves, triggers the secretory activity of these modified ganglionic neurons.
~ Highly innervated tissue that allows for direct CNS regulation of release of
epinephrine (aka adrenaline) and norepinephrine (aka noradrenaline). These are collectively known as catecholamines.
Adrenal medulla secretion
- The adrenal medulla secretes roughly three times as much epinephrine as norepinephrine.
- Their secretion triggers cellular energy utilisation
and the mobilisation of energy reserves. - The metabolic changes that follow catecholamine release are at their peak 30
seconds after adrenal stimulation, and they
linger for several minutes thereafter.
How is cortisol secretion regulated? (Pathway)
- Diurnal Rhythm: Tone set by the suprachiasmatic nuclei in the hypothalamus.
- Triggers: Stress and meals stimulate the hypothalamus.
- Hypothalamus Response: Releases Corticotrophin Releasing Hormone (CRH).
- Pituitary Gland Response: CRH stimulates the pituitary to release ACTH.
- Adrenal Cortex Activation: ACTH stimulates the adrenal cortex to release cortisol.
- Cortisol: Helps manage stress and regulates metabolism.
Hypothyroidism
Hypothyroidism results
from inadequate production of thyroid hormones. In infants, hypothyroidism results in a condition marked by inadequate skeletal and
nervous system development and metabolic rate as much as 40% below normal levels.
Adult hypothyroidism
~ Adult hypothyroidism is known as myxedema and
results in cutaneous swelling, dry skin, hair loss, low body temperature, muscular weakness, and slowed reflexes.
Goiter
~Goiter, an enlargement of the thyroid gland is associated with hypothyroidism. Most goiters develop when the
thyroid gland is unable to synthesise and release adequate amounts of thyroid hormones. However TSH stimulates thyroglobulin production and thyroid follicles enlarge.
Goiter is characterized by a situation where thyroid
continues to produce thyroglobulin but it isn’t processed into T3 and T4 so follicle expands but only low levels of T3 and T4 are released into the circulation
Cause of hypothyroidism
Due to nutritional iodine insufficiency. Can be treated with iodine supplements
~ Another common cause is auto immune response that
generates antibodies that causes destruction of the thyroid follicular cells (Hashimoto’s disease) and so stop T3 and T4 production. Can be treated with replacement therapy.
~ Many similarities with autoimmune destruction of beta- cells in the pancreas and often the same genetic links.
Addison’s Disease
Addison’s Disease results from inadequate stimulation of the zona fasciculata by the pituitary hormone ACTH or from the inability of the adrenal cells to synthesise glucocorticoid hormones.
Individuals lose weight and become pigmented as ACTH is a melanocortin peptide and binds to melanocortin receptors to regulate pigmentation.
Cushing’s Disease
Results from overproduction of glucocorticoids. Adipose tissues in the cheeks and around the base of the neck become enlarged at the expense of other areas,
producing a ‘moonfaced’ appearance.
Hypo/hyperaldosteronism
~Hypoaldosteronism occurs when the zona glomerulosa
fails to produce enough aldosterone. Results in excessive loss of water and sodium ions and drop in blood pressure.
~ Hyperaldosteronism results from too much aldosterone produced. The kidneys retain sodium ions in exchange for potassium ions and this leads to hypertension.
Bile
The release of bile acids assist absorption of lipids and the
digestive enzymes from acinar cells replaces those lost in
stomach and so allows further digestion of food
Circulation of the pancreas
Islets are well supplied with blood capillaries meaning they well placed to sense changes in nutrient levels in the blood.
Importantly this also means beta-cells are well supplied with oxygen which is crucial as glucose stimulated insulin secretion requires the production of high levels of ATP which requires oxidative phosphorylation.
Venules emanate from islets that facilitate the release of hormones to the rest of the body.
Insulin
Decrease blood glucose – limit hepatic glucose output, inhibit glucagon, stimulate glucose uptake by muscles and fat
Amylin
Complements Insulin - Inhibits gastric emptying and glucagon release
Glucagon
Increase blood glucose - liver glycogenolysis and gluconeogenesis
Somatostatin
δ cell
Inhibits insulin and glucagon release and also exocrine release.
Pancreatic Polypeptide (PP)
PP cell (F-cell)
Inhibits exocrine pancreas.
Ghrelin
ε cell
Hunger hormone
Anatomy of blood supply affects how insulin works
Nutrients travel via the hepatic portal vein to the liver where some of the nutrients are absorbed
Some nutrients (including glucose) make it past the liver and are transported in the blood via the heart to the rest of the body including the pancreas.
In response to higher levels of glucose the beta-cells of the pancreas now release insulin which is released into the hepatic portal vein. This increase the uptake and storage of nutrients in liver. Some of the insulin reaches the peripheral circulation where it now stimulates uptake and storage of nutrients into muscle and fat. The net effect of this is to bring glucose levels back down the homeostatic set point levels
Diabetes insipidus - urine
Has no sugar in urine
Diabetes mellitus - urine
Has excess sugar in urine
Diabetes insipidus
~ Diabetes insipidus develops when the pituitary gland no longer releases adequate amounts of antidiuretic hormone (ADH).
~ An individual who develops diabetes insipidus is constantly thirsty, but the fluids consumed are not retained by the body.
Diabetes Mellitus
In diabetes mellitus excess urination is not caused by hormones but by high sugar levels in urine causing hyperosmolarity pulling water into the bladder
Type 1 diabetes:
Primary cause is either loss of, or inadequate insulin production, by the
beta cells of the pancreatic islets usually due to autoimmune mediated
destruction of beta-cells. (parallels to thyroid disease)
Type 2 diabetes:
No autoimmune response but progressive loss of insulin function in target tissues (insulin resistance) requires extra insulin secretion from beta-cells and eventually this causes death of the beta-cells and hence diabetes.
Endocrine function of kidney
Juxtaglomerular cells in kidneys produce renin, an enzyme (often called a hormone). These cells sense
changes in blood pressure and release the renin. This cleaves the pro form of the angiotensinogen to create angiotensin I which is further cleaved to produce angiotensin II and this raises blood pressure.
Kidney fibroblasts also produce erythropoietin, a peptide hormone that stimulates production of new red blood cells. Recombinant forms of EPO are used and misused to increase red blood cell levels.
When blood pressure or oxygen levels in the kidney decline, renin and erythropoietin are produced.
Calcitriol
Calcitriol is a steroid hormone that is active form of Vitamin-D produced in the kidney that contributes to new
bone production.
Its production is stimulated by parathyroid hormone. When
calcium levels fall parathyroid hormone (PTH) levels rise and this increases calcium by stimulating release of calcium from the bone but also by stimulating calcitriol production which stimulates calcium and phosphate ion absorption along the digestive tract to increase calcium
levels.
How is plasma calcium (Ca²⁺) regulated through the Vitamin D pathway?
Vitamin D Sources: Sunlight on skin converts endogenous precursors to Vitamin D; dietary intake includes fortified milk, fish oil, and egg yolks.
Liver Conversion: Vitamin D is converted to 25-hydroxycholecalciferol (25(OH)D₃) in the liver.
Kidney Activation: 25(OH)D₃ is further converted to 1,25-dihydroxycholecalciferol (1,25(OH)₂D₃ or calcitriol) in the kidney.
Parathyroid Hormone Role: Parathyroid hormone (PTH) stimulates the kidney to produce calcitriol.
Calcium Absorption and Release: Calcitriol increases calcium absorption in the bone, distal nephron, and intestine.
Plasma Calcium Increase: This leads to an increase in plasma Ca²⁺ levels.
Feedback Regulation: Elevated plasma Ca²⁺ levels inhibit further release of PTH.
Endocrine function of the heart (ANP)
~ Cardiac muscle cells in the heart produce atrial natriuretic peptide (ANP) and brain natriuretic peptide
(BNP) in response to increased blood pressure or blood volume.
~ ANP and BNP suppress the release of ADH and aldosterone and stimulate water and sodium loss at the kidneys.
Explain the physiological response to increased blood volume involving natriuretic peptides.
Stimulus: Increased blood volume → Atrial stretch.
Integrating Center: Atrial myocardial cells release natriuretic peptides.
Efferent Pathway: Natriuretic peptides travel through the bloodstream.
Effectors and Responses:
Hypothalamus: ↓ Vasopressin.
Kidney: ↑ GFR, ↓ Renin.
Adrenal Cortex: ↓ Aldosterone.
Medulla Oblongata: ↓ Blood pressure.
Systemic Response: ↑ NaCl and H₂O excretion → ↓ Blood volume and pressure.
Acromegaly
Results when an excessive amount of
growth hormone is released after puberty. (after epiphyseal plates have
closed)
Dwarfism
Results from lack of growth hormone. Normal growth patterns can be restored by the injected
administration of growth hormone
Adipose Tissue
Adipose Tissue (colloquially called fat)
* Adipose tissue makes up a large % of body but is often overlooked as mere energy store or padding or insulation. While it does have these functions it is a really crucial tissue with a wider range of functions.
- Adipocytes are specialist lipid storage cells, particularly for triglycerides, because these lipids are toxic in excess in other tissues.
- Two distinct types of adipocyte; white and brown
- Also functions as a connective tissue and plays a role in regulating immune
system and reproductive system - Adipose tissue is made up mainly of adipocytes but also includes blood
vessels and immune cells as well as
fibroblast like cells that can differentiate into adipocytes. - Adipose tissue is found at various locations around the body and each has different characteristics.
- Adipose tissue also produces
hormones that regulate metabolism so can be considered an endocrine organ.
White adipose
The most common type of adipocytes are known as white adipocytes.
* These cells consist of up to 95% stored lipid as triglycerides (shown in yellow in diagram). Note the
nucleus and mitochondria squeezed into a small space by huge amount of triglyceride.
- These look white in most animals but can look yellow in human because we don’t rapidly metabolise carotene and it is lipid soluble so accumulates in this tissue.
- The lipid is contained in a single body and so is said to be unilocular.
- Adipocytes increase or decrease in size depending on amount of lipid stored.
- When “full” can be over 100 μm making them one of biggest cell types in the body.
Adipose varying in size (action of NE and E)
- Adrenaline and noradrenaline stimulate the breakdown of triglycerides, a process known as lipolysis. This releases glycerol and fatty acids which can be used by the rest of the body as sources of energy. Fat cells get smaller
- Insulin block stimulates lipolysis and stimulates triglyceride synthesis and
so promotes the storage of fat. Fat cells get bigger.
White adipose being endocrine cells
Adipocytes are main site for
production of the hormone leptin.
- Leptin levels increase after
feeding and are a signal to the
body that the body has sufficient
nutrient on board. - This is one of the signals that are
integrated in the hypothalamus to
regulate food intake. - It also signal to the body that it is
OK to proceed with functions that
consume a lot of energy e.g. the
immune system and reproduction
Adiponectin
- Adiponectin is a hormone produced in adipocytes that travels to liver and
promotes use of fatty acids for fuel. - This reduces fat load in liver and helps restore it’s responsiveness to insulin.
Brown adipocytes
- A rarer type of adipocyte are called brown adipocytes.
- They are brown in colour because they have a large number of mitochondria and the haem
groups in the electron transport chain of the mitochondria give the overall brown colouring. - The mitochondria in these cells also express uncoupling protein 1 (UCP1) which allow them to generate heat from using fatty acids, thus they are
important in maintaining body temperature. - Exposure to cold increases our number of brown fat cells
- They also differ from white adipose tissue by having many lipid droplets (i.e multilocular)
Subcutaneous fat
- Found in layer immediately under dermal layer or skin that protects the body from the outside world.
- Significant energy store
- Roles in insulation and mechanical padding.
- Also plays an important role in body shape as it plays a big role in how we look.
- Important feature is that the arteries and veins in this depot link it to the systemic circulation and this is thought to be why it is less dangerous than some types of intra abdominal fat.
Intra-abdominal fat
(also called visceral fat)
- Actually describes a range of adipose depots found inside the abdomen (i.e excludes subcutaneous)
- The biggest depots are within the peritoneum (the membrane that lines the abdominal cavity) so sometimes these depots are collectively referred to as intraperitoneal depots.
- The two anatomically distinct large fat depots within the peritoneum
- omental associated with the omentum which is the anterior (front) side of the peritoneum and resembles an apron like structure over gut and liver.
- mesenteric associated with the mesenteries (the structures that hold the digestive tract in place)
- Fat depots outside peritoneum are called retroperitoneal adipose tissue and includes the fat depots attached to the kidney.
Dermal adipocytes
- Some adipocytes can be found in the dermal layer
- Not a large number so not a major energy store
- Evidence indicates they play a role in wound healing
- Also secrete antibacterial peptides so appear important in innate immune responses
- Evidence suggests they support hair follicle development
Adipose in heart
- Provides localized supply of
fatty acids for heart
function. - In obesity the size of this
adipose tissue increases
and this impacts negatively
on cardiovascular function.
Bone marrow adipocytes
- Lots of adipocytes in bone marrow.
- These are different from standard white adipocytes as the are multilocular.
- Their function not fully understood.
Adipocytes in the mammary gland
- The mammary gland contains a large number of white adipocytes.
- Mammary adipocytes can
directly exchange lipids with milk producing cells so important for milk production. - The mammary adipose tissue
depot changes during pregnancy to facilitate this by differentiating white
adipocytes into milk producing cells call pink adipocytes.
Ectopic fat distribution
- In normal circumstances in lean people most lipid is in adipocytes but
in obesity the ability of these cells to store lipid is maxed out and so lipid starts to deposit in other tissues. This is called ectopic fat. - Thus, the expansion of adipose depots is initially a good thing as it
protects other tissues from harm - The next place lipid accumulated is in liver and this can develop into a
condition called fatty liver but can also accumulate between muscle.
Lipodystrophy
- This is a condition causing inability to properly store lipid in adipocytes
- Can be caused by genetic defects in adipose tissue, autoimmune mechanisms or as a side effect of some drug treatments.
- Can affect different fat depots differently and so have strange
effects on body shape. - Dangerous as the fat starts to accumulate ectopically in other tissues instead and causes major problems.
Liposuction
- Commonly used practice to
remove fat and reshape body
contours. - Only removes subcutaneous
fat so doesn’t really solve
impacts of adiposity on
metabolic disease.
Bariatric surgery
- Reducing the size of the stomach with sleeve gastrectomy or
bypassing the duodenum with Roux-en-Y bypass provides long
term sustainable weight reduction in most patients. - Mainly works by reducing food intake.
Drugs
Mimic action of GLP-1, reduce hunger
What controls release of sex hormones?
HPG axis controls sex hormone release.
Daily, monthly, life-cycle rhythms.
Explain the role of Gonadotropin-releasing hormone (GnRH) and gonadotropins in spermatogenesis.
Hypothalamus: Releases GnRH.
Anterior Pituitary: GnRH stimulates the release of gonadotropins (LH and FSH) from gonadotropes.
LH (Luteinizing Hormone): Stimulates Leydig cells in the testes to produce testosterone.
FSH (Follicle-stimulating Hormone): Works with testosterone to stimulate Sertoli cells and support spermatogenesis.
Spermatogenesis Process:
Occurs in seminiferous tubules.
Stages:
Spermatogonia (initial stage).
Primary and secondary spermatocytes.
Spermatids.
Mature spermatozoa.
Involves complex interactions within the seminiferous tubules, including support from Sertoli cells and regulation of the blood-testis barrier.
Regulation of Male Reproductive Hormones
Anterior Pituitary releases LH and FSH.
LH stimulates Leydig cells to produce testosterone.
FSH targets Sertoli cells (nurse cells) to support spermatogenesis.
Sertoli cells produce inhibin to inhibit FSH, regulating spermatogenesis.
Testosterone is essential for male secondary sexual characteristics and spermatogenesis.
Regulation of Female Reproductive Hormones
Anterior Pituitary releases LH and FSH.
LH stimulates Thecal cells to convert cholesterol into androgens.
FSH targets Granulosa cells to convert androgens into estradiol.
Granulosa cells produce inhibin to inhibit FSH, regulating hormone levels.
Estradiol and progesterone are essential for female reproductive functions.
Estrogens
The ovaries make most of the estrogen hormones, although
the adrenal glands and fat cells also make small amounts of
the hormones.
The four major naturally occurring estrogens in women are
* estrone (E1) predominant during menopause
* estradiol (E2) predominant pre menopause
* estriol (E3) predominant during pregnancy
* estetrol (E4) only during pregnancy
Males have small amounts of estrogens from testes as well as
various peripheral tissues. Testosterone can be converted
into estrogen
Reproductive actions in the female of estrogen:
Estrogen levels rise during puberty to promote:
* oogenesis and follicle growth
* Maturity of uterine tubes, uterus, and vagina
* Growth of the breasts
* Widening and lightening of the pelvis
At sexual maturity
* Estrogen – follicle maturation
Non-reproductive actions of oestrogen in the female:
*Increased deposition of subcutaneous fat
*Growth of axillary and pubic hair, female sexual behaviour.
Progestins
Progesterone is the main progestin and is produced by the corpus luteum, a transitionary structure formed from the follicle once an oocyte is released. The corpus luteum is formed of granulosa cells that release progesterone, and this defines the luteal phase of the ovarian cycle.
- Progesterone prepares the uterus for implantation and prepares the mammary glands for lactation.
If pregnancy occurs:
* Human chorionic gonadotropin (hCG) levels increase, and this maintains the corpus luteum, maintaining elevated progesterone.
* At 12-weeks gestation, the placenta takes over the task of producing progesterone.
* After birth, progesterone falls.
No pregnancy:
* Corpus luteum degenerates and progesterone falls. Males have almost no progesterone – any in the body gets converted to testosterone in the testes
Testosterone
Although gonadotropins and sex hormones in males are not thought to cycle like in females, testosterone does have a daily cycle (higher in the morning).
Reproductive actions in the male:
* Necessary for fetal development of male external genitalia
* Promotes production of functional sperm
* Maintains secretory glands of the male reproductive tract
Non-reproductive actions:
* Appearance of pubic, axillary, and facial hair, enhanced growth of the chest, deepening of the voice, male sexual behaviours
* Bones grow and increase in density
* Skeletal muscles increase in size and mass
Females also produce small amounts of androgens. Dehydroepiandrosterone (DHEA) DHEA is a relatively weak androgen produced by the adrenals and ovaries/testes
Steroid hormone receptors
- Estrogen receptor (ER), androgen receptor (AR), progesterone receptor (PR) and glucocorticoid receptor (GR) are all steroid hormone receptors.
- Nuclear receptor superfamily
- Transcription factors that can bind to recognition motifs on DNA and induce expression of a specific suite of genes upon activation by ligand (steroid hormone).
- Co-repressors and co-activators can alter their activity.
Crosstalk (e.g. glucocorticoids and estradiol)
- Glucocorticoids can inhibit estradiol from binding ER
- Estradiol can inhibit activation of GR by inhibiting its phosphorylation.
- Estradiol can also promote degradation of GR.
- Large overlap in DNA binding sites for these receptors, therefore they can interfere in each other’s activities.
Clinical implications for sex hormone cross talk with GC
- Corticosteroids also important for early development of organs important for metabolic health (pancreas beta cells, skeletal muscle, adipose and liver).
- Corticosteroids critical for maturation of lungs and heart therefore antenatal corticosteroid therapy (ACT) for pregnancies with risk of preterm delivery.
- However, exposure to elevated glucocorticoids antenatally, endogenous (stress) or pharmacological, causes metabolic issues later in life. ‘Developmental misprogramming’
- GCs can inhibit estrogen which we have noted as being metabolically protective in females.
- This crosstalk has also been linked to stress induced cardiovascular disease risk.
Sex-specific health considerations (females)
Pregnancy and pregnancy complications
* Gestational diabetes
* Pre-eclampsia
* Hyperemesis Gravidarum
Symptoms associated with menstruation (especially in puberty)
Symptoms associated with menopause
* Osteoporosis – 80% female
Sex-specific health disorders (females)
Female-specific disorders/disorders that are more common in females:
* Endometreosis
Hypogonadism, low estrogen - failure in hypothalamus-pituitary-gonadal system resulting in low
sex hormones
* Primary (hypergonadotropic hypogonadism),
* Secondary (hypogonadotropic hypogonadism)
Polycystic ovary syndrome (PCOS) – hyperandrogenism.
Cancer of the female reproductive system
Autoimmune disease
Thyroid disease
Sex-specific health considerations (males)
Hypogonadism, undeveloped or underdeveloped male genitals if occurs developmentally or pubertally.
Impaired reproductive function if later in life.
* Primary (hypergonadotropic hypogonadism),
* Secondary (hypogonadotropic hypogonadism)
Cancer of male reproductive system
X-linked disorders (e.g. hemophilia)
Sex and cardiovascular disease
Ischemic heart disease: Myocardial Infarction (MI)
- Obstructive coronary artery disease is more common in males (classic heart attack symptoms). (Pre-menopausal women protected from atherosclerosis.)
- Females more likely to have microvascular dysfunction resulting
in chronic MI/ischemic heart disease a.k.a angina (silent heart attack).
Heart failure and sex
HF with with preserved ejection fraction (normal systolic function) x2 more prevalent in females (smaller
stiffer hearts).
-Estrogen protects against cardiac inflammation.
Hypertension is larger risk factor for females
Males have HF with reduced ejection fraction due to adverse cardiac remodeling.
-Testosterone linked to adverse cardiac remodeling
Although HF more prevalent in females (over 70 years old), Females have generally better outcome.
Pre-menopausal females are protected from metabolic disease.
- Male peak diabetes prevalence 65-69 years
- Female peak diabetes prevalence 70-79 years
- OR diabetes 1.7 for males
- Elevated FPG more prevalent in males, impaired glucose tolerance more prevalent in females*
Effects of Estrogen in Females
Liver: Enhanced glucose uptake (better insulin sensitivity)
Adipose Tissue:
Higher overall body fat
More subcutaneous vs visceral and ectopic fat storage
Preserved and active brown fat
Increased leptin sensitivity (mice) = reduced food intake
Muscle:
Lower muscle mass
Higher mitochondrial activity
Enhanced glucose uptake (better insulin sensitivity)
Pancreas:
Enhanced insulin synthesis and secretion
Protection of beta cells from oxidative stress and lipotoxicity
Gastrointestinal Tract: Enhanced incretin (GLP-1) response
Estrone
E1, predominant during menopause
Estradiol
E2, predominant pre menopause
Estriol
E3, predominant during pregnancy
Estetrol
E4 only during pregnancy
IGF-1 action on immune system
Thymus development and function
Haematopoiesis
Immune cell function
IGF-1 action on kidney
Glomerular development and integrity
IGF-1 action on fetus
Fetal growth and differentiation
IGF-1 action on placenta
Placenta growth and development
IGF-1 action on reproductive organs
Ovarian folliculogenesis
Testicular function and integrity
IGF-1 action on brain
Neuronal development myelinization and protection
B-amyloid clearance
Antinflammatory
IGF-1 action on heart
Cardiovascular development and protection
Vasodilator
IGF-1 action on muscle
Muscle growth and development
IGF-1 action on bone
Normal bone growth
