Week 17 Flashcards
What are the main endocrine glands?
Hypothalamus,
Pituitary,
Pineal,
Thyroid,
Parathyroid,
Adrenal
What are the main endocrine-expressing tissues/organs?
Thymus,
Pancreas,
Ovary,
Testis
Main control mechanisms of the endocrine system?
Feedback mechanisms,
Signals from nervous system,
Chemical changes,
Presence of other hormones
What do tropic hormones act on? What do Trophic hormones do?
Tropic: act on endocrine glands
Trophic: stimulate growth (hypertrophy)
What do hormones do? By initiating what?
Stimulate change by initiating:
- Synthesis of new molecules,
- Changes in permeability of cell membranes,
- Changes in transport of a substance into or out of the cell
- Changes in the rate of metabolic actions
- Contraction of a smooth or cardiac muscle
Hypothalamus and pituitary glands are very closely connected: anatomically and functionally. The pituitary glands are also known as:
Neurohypophesis (Posterior = PP)
Adenohypophesis (Anterior = AP)
Anterior structure of the hypothalamus?
- Secretes releasing (RH) or inhibiting hormones (IH) into hypothalamo - hypophyseal portal system
- RH and IH move to the anterior pituitary and influence the release of other hormones
- Anterior Pituitary synthesis hormones
Posterior structure of the hypothalamus?
- The hypothalamus connects to the pituitary gland via the infundibulum
- The supra optic and paraventricular nuclei in the hypothalamus synthesise hormones and release them into the inferior hypophyseal artery in the posterior pituitary
- The neurons form the hypothalamic-hypophyseal tract
What does the hypothalamus do?
- Release inhibitory or releasing hormones to control the release of Anterior Pituitary hormones
- Synthesis of AntiDiuretic Hormone and Oxytocin (released by posterior pituitary)
- Neural control of adrenal gland and release of adrenaline and noradrenaline (sympathetic control via preganglionic motor fibres)
What are the two types of inhibiting hormones?
Growth hormone Inhibitory Hormone (GHIH)
Prolactin-inhibiting Hormone (Dopamine) (PIH)
What are the five types of releasing hormones?
Growth Hormone Releasing Hormone (GHRH)
Thyrotropin Releasing Hormone (TRH)
Gonadotropin Releasing Hormone (GnRH)
Corticotropin Releasing Hormone (CRH)
Prolactin Releasing Hormone (PRH)
Anterior pituitary structure consists of Pars Tuberalis, Pars Distalis and Pars Intermedia. What are these?
Pars Tuberalis:
Wraps around infundibulum
Pars Distalis:
Largest, most distal portion
Most AP hormones released from here
Pars Intermedia:
Narrow region on edge of Posterior
Releases Melanocyte Releasing Hormone
Hypophyseal Portal System moves hormones from the ______ to the ______ _____ and into the ______ ______
Hypothalamus
Anterior Pituitary
Blood stream
Explain what occurs after the stimulation of the hypothalamus: positive feedback cycle?
- Hypothalamic neurones release releasing hormones or inhibitory hormones into Primary Capillary Plexus
- Hormones travel through portal veins to Anterior Pituitary (AP)
- AP secretes hormones into Secondary Capillary Plexus
- Plexus empties into general circulation
What hormones are in the anterior pituitary, what secretes them?
Human growth hormone, secreted by somatotrophs
Thyroid-stimulating hormone, secreted by thyrotrophs
Follicle-stimulating hormone, secreted by gonadotrophs
Luteinizing hormone, secreted by gonadotrophs
Prolactin, secreted by Lactotrophs
Adrenocorticotropic hormone, secreted by cortiocotrophs
Melanocyte-stimulating hormone, secreted by corticotrophs
What are direct actions (metabolic) of growth hormones?
- Increases blood levels of fatty acids; protein synthesis
- Decreases rate of glucose uptake and metabolism thus conserving glucose
- Glycogen breakdown and glucose release to blood (anti-insulin effect)
What are the indirect actions of growth hormones?
- Mediates growth via growth-promoting proteins (Insulin-like Growth factors)
- IGFs stimulate: uptake of nutrients, DNA and proteins. Formation of collagen and deposition of bone matrix
- Major targets - bone and skeletal muscle
What factors may increase growth hormone secretion include:
Sleep
Physical stress
Exercise
Low blood glucose
What problems may occur with growth hormone regulation?
Hypersecretion - results in Acromegaly in Adults (pituitary tumour) and Gigantism in Children
Hyposecretion: Pituitary dwarfism in children
What are the symptoms of Acromegaly (pituitary tumour) in adults due to hypersecretion of growth hormones?
Enlarged hands and feet,
Fatigue and muscle weakness
What are the symptoms of Gigantism in children due to hypersecretion of growth hormones?
Large hands and feet,
Prominent jaw and forehead
What are the symptoms of Pituitary dwarfism in children due to hyposecretion of growth hormones?
Below average growth
What does the hormone Prolactin do?
Prolactin (and progesterone) promote lobule growth (Oestrogen promotes ductal growth)
Nipple stimulation activated hypothalamus to inhibit PIH (dopamine)
Prolactin increases milk production
Role of Melanocyte Stimulating Hormone?
Regulated pigment cells in amphibians, fish, reptiles and some mammals
Role in satiety in humans
Increases with ACTH production leading to hyperpigmentation in adrenal gland disorders.
Stimulation of the arcuate nucleus (ARC) in the hypothalamus can result in changes in what?
Control of food intake
(Ghrelin from stomach stimulated ARC nuclei resulting in increased appetite, while POMC stimulates increased Melanocyte stimulating hormone reducing individuals appetite.)
What does (Adreno)corticotrophin hormone (ACTH) do?
Acts on adrenal gland (tropic) to stimulate release of glucocorticoids.
Cortisol and glucocorticoids involved in regulating glucose availability
Glucocorticoids inhibit CRH and ACTH
What is (Adreno)corticotrophin hormone (ACTH) release stimulated by?
Stimulated release by CRH (Corticotrophin releasing hormone) from hypothalamus
What is the posterior pituitary’s job?
Storage and release of hormones produced in the hypothalamus
(supraoptic and paraventricular neurosecretory cells)
What is oxytocin (posterior pituitary hormone)?
Oxytocin increases at night. Labour often initiated at night.
Stimulates milk ejection (let-down reflex)
Also involved in control of reproductive behaviours:
- Pair bonding
- Maternal care
- Sexual activity
What is Anti-diuretic hormone (posterior pituitary hormone)?
(Vasopressin)
- Controls water balance
- Decreases urination
- Increases water absorption
When is Anti-diuretic hormone (posterior pituitary hormone) released?
In response to low blood pressure, blood volume or an increase in solute concentration
Hypothalamus development in embryo’s?
Forms from a proliferation of neuroblasts in the diencephalic walls (part of the forebrain)
Formation of mammillary bodies: pea-like swellings on the ventral surface of hypothalamus will become the endocrine centres.
When is the hypothalamus clearly detectable in an embryo?
A hypothalamus is clearly detectable by 3 months
Pituitary gland development step 1?
Infundibulum and Rathke’s pouch develop from neural ectoderm and oral ectoderm, respectively.
Pituitary gland development step 2?
Rathke’s pouch completely constricts at base;
Rathke’s pouch completely separates from oral epithelium;
Structures continue to grow towards and round each other.
What is Adenohypophysis formed by in pituitary development?
Pars distalis, pars tuberalis, and pars intermedia. (Rathke’s pouch during pituitary development)
What is Neurohypophysis formed by in pituitary development?
Development of pars nervosa, infundibular stem and median eminence.
What is the thyroid gland composed of?
Lobular structure joined by an Isthmus (bridge)
Tissue composed of Follicles
What do Parafollicular cells and follicular cells secrete in the thyroid gland?
Parafollicular secrete Calcitonin
Follicular cells secrete Thyroxin (T3 and T4)
What are follicles of the thyroid filled with?
Thyroglobulin, forming a collid
Which gland is the only gland to store a large amount of hormone? Which hormone is lipid soluble?
- Thyroid gland is the only gland to sore large amounts of hormone
- Thyroxin is lipid soluble
What stimulated the movement of iodine into thyroid follicles?
What other features does iodine have in thyroid hormones?
Thyroid stimulating hormone stimulates movement of iodine into thyroid follicles by active transport.
Iodine is then added to Thyroglobulin
Thyroxine (T3 and T4) have multiple iodine atoms
T4 is less active, can be converted to more active T3 in target cells
Activation of thyroid hormones, step 1?
Iodine trapping - follicular cells actively transport iodine from the blood into the cytosol
Activation of thyroid hormones, step 2?
Follicular cells also synthesise thyroglobulin (involves rough ER and Golgi Body) which is then released into the lumen of the follicle
Activation of thyroid hormones, step 3?
Negatively charged iodide ions are oxidised to I2 molecules, which then also pass into the follicular lumen
Activation of thyroid hormones, step 4?
Some of the tyrosine molecules that form thyroglobulin become iodised (if bound 1 iodine atom, its called moniodotyrosine (T1) if bout to 2 iodine atoms, diiodotyrosine (T2))
Activation of thyroid hormones, step 5?
T1 and T2 molecules can join up to create T3, or T2 molecules can join to other T2 molecules to form T4
Activation of thyroid hormones, step 6?
The iodised material (colloid) is taken back into the follicular cells by pinocytosis; it is then digested by enzymes, leaving molecules of T3 and T4
Activation of thyroid hormones, step 7?
T3 and T4 are lipid soluble, and diffuse into the blood
Regulation of thyroid hormone release (step 1 & 2)?
- Low blood levels of T3 and T4 / low metabolic rate stimulates release of TRH.
- TRH carried by hypophyseal portal veins to anterior pituitary, stimulates release of TSH by thyrotrophs
Regulation of thyroid hormone release (step 3, 4 and 5)?
- TSH released into blood stimulates thyroid follicular cells,
- T3 and T4 released into blood by follicular cells
- Elevated T3 inhibits release of TRH and TSH (negative feedback)
Systemically, what does the thyroid hormone do?
Increases basic metabolic rate by stimulating the use of O2 to make ATP
Increases synthesis of sodium/potassium pumps: use of ATP increases body temp
Stimulates protein synthesis (anabolism)
Accelerate body growth with GH: nervous and skeletal systems
Stimulates erythropoietin (RBC) production
Developmentally, what does thyroid hormone do?
Involved in metamorphosis in amphibians
Development of ovarian tissue and egg release
Brain development
Bone growth and development
Congenital hypothyroidism
Symptoms of hyperthyroidism?
Tachycardia (rapid heart rate)
Tremors
Warm, moist skin
Proximal muscle weakness
Gynecomastia in males
Goiter
Symptoms of hypothyroidism?
Slow Heart rate, increased Blood pressure
Low body temperature
Dry hair and skin
Lethargy and weakness
Reduced alertness
Puffiness in face
Goiter
Gestational hypothyroidism difficult to differentiate
What are the signs of Grave’s Opthalmology Disease (Autoimmune disorder due to not treating hyperthyroid)
the proteins and connective tissue within the eye socket are often targeted by the same autoimmune antibodies as the thyroid gland
Inflammation, swelling and scarring causes the eyes to bulge forwards (exophthalmos) and the eyelids to retract
There may also be ulceration of the cornea and/or damage to the optic nerve
What are the signs of Thyroid Acropachy (Autoimmune disorder due to not treating hyperthyroid)?
Swelling of soft tissue and finger clubbing
Thought to be due to involvement of autoimmune antibodies – cause unclear
Usually only seen in moderate-severe disease
What is the role of Calcitonin?
Maintains Calcium homeostasis by increasing calcium uptake into bones
Decreases blood calcium levels
Role in bone growth and maintenance of density
Calcitonin from Salmon is used to treat what?
Osteoporosis
What is calcitonin released by?
Parafollicular cells in thyroid
Where is the parathyroid gland located?
Behind the thyroid gland in pairs
What does the parathyroid gland secrete?
Parathyroid hormone
What composes the parathyroid gland?
Chief cells (secrete PTH)
Oxyphils (Unknown role)
Actions of Parathyroid hormone (PTH) on bone: regulating blood calcium?
Increases number and activity of osteoclasts (bone chewinng)
Bone resorption increases, so calcium and phosphates are released into the blood
Bones are a Calcium reservoir
Actions of Parathyroid hormone (PTH) on kidneys: regulating blood calcium?
Slows the rate of loss of calcium and magnesium from blood into urine (so blood levels increase)
Increases loss of phosphate from blood into urine (so blood level decreases)
Promotes formation of the hormone CALCITRIOL (active form of vitamin D) in the kidneys, which increases the rate of calcium, phosphate and magnesium absorption from the GI tract into the blood
Interaction between thyroid and parathyroid hormones step 1?
High level of Ca2+ in blood stimulates thyroid gland parafollicular cells to release more Calcitonin
Calcitonin inhibits osteoclasts, thus decreasing blood Ca2+ level
Interaction between thyroid and parathyroid hormones step 2?
Low level of Ca2+ in blood stimulates parathyroid gland chief cells to release more PTH.
PTH promotes release of Ca2+ from bone extracellular matrix into blood and slows loss of Ca2+ in urine, thus increasing blood Ca2+ level
Interaction between thyroid and parathyroid hormones step 3?
PTH also stimulates kidneys to release calcitriol
Calcitriol stimulates increased absorption of Ca2+ from foods, which increases blood Ca2+ level
Where is the adrenal gland located?
What are the two regions surrounded by a capsule called?
Sits above the kidney
Split into regions surrounded by a capsule:
Outer cortex,
Inner medulla
What are the 4 different zones of the adrenal gland?
Zona glomerulosa
Zona fasciculata
Zona reticularis
Medulla
Role of Zona glomerulosa in the adrenal gland?
Stimulates Mineralocorticoids that regulate mineral homeostasis
Role of Zona fasciculata in adrenal gland?
Stimulates Glucorticoids that regulate glucose homeostasis
Role of Zona reticularis in the adrenal gland?
Stimulates Androgens that regulate pubic hair and prepubertal growth, source of female androgen/Oestrogens in postmenopausal women
Role of medulla in adrenal gland?
Stimulates Hormones: adrenaline and noradrenaline. These Intensify responses of sympathetic NS
What is the major mineralocorticoids secreted by the adrenal gland? What is its role?
Aldosterone
- helps regulate sodium and potassium homeostasis; it also promotes excretion of H+ into the urine: therefore it helps prevent acidosis
- Regulates blood volume, blood pressure and blood levels of Na +, K+ and H+
What pathway controls secretion of aldosterone?
The renin-angiotensin-aldosterone (RAA) pathway
The renin-angiotensin-aldosterone (RAA) pathway in the adrenal cortex?
- Increased aldosterone
- In kidneys, increased Na+ and H2O reabsorption and increased secretion of K+ and H+ into urine
- Increased blood volume
- Blood pressure increases until it returns to normal
What are the several roles of glucocorticoids in the adrenal gland?
- Increase rate of breakdown of proteins
- Increases rate of gluconeogenesis in liver
- Increases rate of lipolysis, releasing fatty acids into blood
- Depresses immune response
- Decrease REM sleep and increases slow-wave sleep (can cause insomnia and mood changes if high)
- Sensitise blood vessels to vasoconstriction causing hormones
- Inhibit WBC that participate in inflammatory response, tissue repair and slow wound healing
What is the major androgen secreted by the adrenal cortex?
What is its role in males versus females?
Dehydroepiandrosterone (DHEA)
Males = after puberty hormone testosterone is secreted in much larger quantities so DHEA has virtually no effect
Females = DHEA and other adrenal androgens play major role in promoting libido and are converted to oestrogens. In post- menopausal women, all oestrogens come from adrenal androgens
The adrenal medulla is stimulated by what?
Sympathetic preganglionic neurons of the autonomic nervous system
The adrenal medulla enhances autonomic nervous system response, how?
Releases Catecholamines: adrenaline, noradrenaline
- Glucose release from glycogen breakdown
- Increase heart rate
- Dilate airways and increase respiratory rate
- prepare to run or fight…
What is Eustress: The stress response?
helpful, everyday stress that prepares us to meet challenges
What is distress: the stress response?
Any type of harmful stress that may be damaging
The flight-fight-freeze response is the first stage of the stress response, what is this?
Stimulates the body’s resources to prepare for immediate activity. Adrenaline and noradrenaline
What is the resistance reaction: the stress response?
the second stage in the stress response and lasts longer than the fight-or-flight response. Cortisol and glucocorticoids
Cortisol may increase due to stress, why is this beneficial?
- More glucose availability provides rapid source of energy to meet homeostatic requirements
- Blood vessels become more sensitive to hormones that cause vasoconstriction; so blood pressure increases, increasing perfusion of organs and delivery of O2 and nutrients
Development of the internal ad external reproductive system is controlled by…?
Genotype (XX or XY usually) and Hormones
Primary sex determination: creating a gonad?
- Primordial Germ Cells migrate from the yolk sac into the urogenital ridge at ~ week 6 creating ovarian and testicular tissue.
- Gonadal tissue can now start to express hormones:
Ovary = oestrogen
Testes = Testosterone
Internal sexual development differentiation: all embryos?
All start with bipotential internal and external anatomy, hormonal exposure leads to a maintenance and degeneration of structures: 2 sets of ducts to one.
Internal sexual development differentiation: xx?
At 20 weeks XX
- A lack of testosterone leads to degeneration of Mesonephric duct (Wolffian)
- Oestrogen (and receptors) maintains the Paramesonephric duct
- Remaining Paramesonephric duct becomes the oviducts, uterus and upper part of the vagina
Internal sexual development differentiation: XY?
In XY foetuses at 16 weeks:
- Anti-Mullerian Hormone stimulates degeneration of Paramesonephric ducts
- Testosterone (and receptors) maintains mesonephric duct
- Mesonephric duct becomes the epididymis and vas deferens
Development of external genitalia?
- At early stages the external genitalia is visible as a genital tubercle
- At 7 weeks the genital tubercle is bigger in females than males
- This can lead to mistaken sex assignation in early prenatal scans
External sexual differentiation: XX growth due to oestrogen
- Genital tubercle becomes the clitoris
- Genital fold becomes the Labia minora and urethral and vaginal orifices
- Genital swelling becomes the Labia majora
External sexual differentiation: XY growth due to Dihydrotestosterone
- Genital tubercle becomes the glans penis
- Genital fold forms the urethral fold and raphe
- Genital swelling forms the scrotum
What are the hormones most often associated with sexual development, puberty and function?
- Androgens: testosterone from testes and adrenal cortex
- Oestrogen: ovaries, placenta, testosterone
- Progestins: ovaries and placenta
XX and XY systems use the same hormones, however variations in form and function of the body are related to:
- Quantity
- Structures present
- Receptors and mediators
Puberty: initiation of the reproductive cycle. Step one?
As the brain matures, it starts to produce Gonadotrophin releasing Hormone (GnRH) from the hypothalamus.
Puberty: initiation of the reproductive cycle. Step two?
Gonadotrophins are released from the Anterior Pituitary
Luteinising Hormone (LH)
Follicle Stimulating Hormone (FSH)
Puberty: initiation of the reproductive cycle. Step three?
LH and FSH stimulate gonadal development and the release of Testosterone, Oestrogen and Progesterone
Puberty: initiation of the reproductive cycle. Step four?
T, E and P have effects on the function of the reproductive tissues and the system:
1. Growth
2. Secondary sex characteristics
Hormone levels are controlled by negative feedback.
The female reproductive cycle controls three main activities relating to fertility. These are:
- Ovarian cycle (Maturation of the oocyte)
- Uterine cycle (suitable implantation environment)
- Cervical cycle (controls sperm entry)
What are female gonads?
Female gonads (ovary) are a site of endocrine production. Also produces growth factors and regulatory peptides
Female reproduction is influenced by _____ more than the male reproductive system. May be related to up to ____% of cases of female ______.
Stress
50%
Infertility
Meiosis and ovum formation?
Occurs before sperm and ova formation
Generation of 4 daughter cells from the original, via 2 successive cell divisions
Each “daughter” has half the number of chromosomes of the original cell
Oocyte meiosis produces one daughter and one polar body, which degrades
Source of genetic diversity: “crossing over”
Full chromosome number restored at fertilisation after meiosis II and ovum formation
Ovulation and oogenesis 1?
Oocytes are surrounded by follicular cells that provide a supportive function and release hormones to drive the cycle
Ovulation and oogenesis 2?
Rising hypothalamic Gonadotrophin releasing hormones (GnRH) levels stimulate production of follicle stimulating hormone (FSH) and Luteinising hormone (LH) from the anterior pituitary.
Ovulation and oogenesis 3?
FSH stimulates growth of follicular cells and therefore production of oestrogen. More cells = more oestrogen
LH stimulates cells to produce androgens and ovulation
Uterine cycle: Proliferative phase (follicular)?
- Oestrogen levels increase from maturing follicles
- Oestrogen activity increases growth of the uterine lining to prepare for implantation
- Oestrogen stimulates GnRH (and FSH and LH)
Uterine cycle: Secretive phase (Luteal)?
Progesterone and oestrogen activity:
- Inhibition of FRH and LH release by Inhibin and Progesterone with Oestrogen
- Progesterone from maturing follicles, then the corpus luteum after ovulation
- P and O increase growth of uterine lining
- P stimulates secretion of nutritive substance to support early life
What is the Periovulatory / Ovulatory phase of the cervical cycle?
Oestrogen increase changes mucus fibres to a more linear conformation to allow sperm to follow the fibres up.
Consistency of mucus is more fluid and slippery
Mucus alkaline to promote sperm survival
Sperm can survive several days in cervix. (increases fertile window)
What is the Luteal phase of the cervical cycle?
Progesterone thickens cervical mucus to create a cervical plug, trapping sperm
pH changes
Female hormone cycle summary?
Increased FSH and LH from Anterior pituitary follicle and egg maturation
Follicle secretes oestrogen (O): initially decreasing FSH and LH
Increased O induces FSH and LH spike: ovulation
O decrease as not produced by follicle
Corpus Luteum takes over O and Progesterone production increases: uterine development
Corpus Luteum degradation: dec P and O. Inhibin decreases, LH and FSH increases
Decreases P and O
Production of sperm is also known as what?
Spermatogenesis
Spermatogenesis can take 65-75 days, depending on the individual, is genetically controlled and consists of 6 different stages. Which are?
A-spermatogonium
B-spermatogonium
Primary spermatocyte (= spermatocyte order I)
Secondary spermatocyte (= spermatocyte order II)
Spermatid
Sperm cell (= spermatozoon)
The number of spermatogonic stem cells stimulates is controlled by what system?
Endocrine
What are Leydig and Sertoli cells?
Leydig = Testosterone production
Sertoli / Sustentacular cell = Tree shapes (alters shape), extends from basal lamina to lumen, supportive of germ cell development, phagocytosis of excess fluid
Hormonal changes are one of the first indicators of pregnancy. What is the Early Pregnancy Factor?
Found in the blood stream within hours of conception. Its an immunosuppressant and helps to stimulate trophoblast (placental) growth during the peri-implantation period
Maternal menstrual and “pregnancy” hormone change:
Increase in Progesterone, oestrogen and human chorionic Gonadotrophin (pregnancy maintenance)
Decrease in Gonadotrophin releasing hormone, follicle stimulating hormone and luteinising hormone (stops ovulation)
What are the first key events of pregnancy?
Maintenance of pregnancy and Formation and growth of the placenta
Pregnancy hormones are initially released by the corpus luteum after ovulation and the key hormones are:
- Human Chorionic Gonadotrophin
- Progesterone
- Oestrogen
(Placenta will take over production from CL)
