Endocrine Axes & Homeostatic Feedback Flashcards
What is endocrinology in its simplest form?
- Communication between at least three organs (hypothalamus, pituitary gland and peripheral organs)
- First gland sends message
- Second releases hormone into blood
- Third in periphery responds to hormone
What is the purpose of hormones?
- Chemical messengers to respond rapidly to physiological or environmental cues (danger)
- Act on organs and tissues throughout body (regulate internal physiology and behaviour like freeze-fight-flight)
Describe Endocrine glands
-Do not have ducts
=products secreted directly into blood:
=e.g. pituitary, thyroid, adrenal, parathyroid glands, gonads (testis & ovaries)
Describe Exocrine glands
-Products secreted via ducts to epithelial surfaces inside or outside the body:
=e.g. sweat, salivary, mucus, mammary gastric, prostate glands, liver bile duct
How can the pancreas have both endocrine and exocrine functions?
-Endocrine:
=insulin, glucagon, somatostatin & pancreatic polypeptide
-Exocrine:
=digestive enzymes secreted via pancreatic duct to the small intestine
What are the types of endocrine hormone signalling?
-Classical
=Hormone carried by blood
=Receptors on target cells
-Paracrine (local) signalling =Hormone diffuses through tissue fluids =To receptors on target cells-Autocrine (local) signalling =Hormone diffuses through tissue fluids =To receptors on same cell
-Intracrine signalling
=Inactive prohormone enters a cell
=Activated intracellularly (sex steroids like oestrogen)
What are the different types of hormone receptors?
- Peptides (surface receptors- GPCRs or receptor kinases)
- Steroid (cholesterol backbone, less soluble, intracellular, transported on plasma carrier proteins)
- Amine (transported on plasma carrier proteins)
How can hormone receptors be drug targets?
- Steroid receptors= 30% pharma drug targets
- GPCR= 40% pharma drug targets
What are the types of peptide hormones?
-Hypothalamic-releasing hormones
=pass through hypothalamic portal circulation and bind to receptors on specific anterior pituitary cell types)
-Pituitary ‘trophic’ hormones (growth promoting effects)
-Target organ peptide hormones (adrenal medulla catechol-amines acting on vasculature)
Describe peptide hormone action
- Bind to plasma membrane receptors (do not enter cell)
- Act quickly by activating G-proteins
- Generate a chemical second messenger signal (cAMP, Ca2+, protein kinase activation)
What are the classical actions of steroid hormones?
(1) Steroids transported in blood bound to ‘carrier’ proteins.
(2) Diffuse through plasma membrane of target cells bind to inactive cytoplasmic steroid receptors
(3) Activated ‘transcription factor’ enters the nucleus binds to ‘control regions’ activating gene transcription
(4) mRNA leaves the nucleus → new cytoplasmic protein synthesis
* takes time to activate (24-48 hrs)
What is the diffuse endocrine system and what hormones do the organs make?
-Not the classical endocrine glands
- Kidney= RAAS, Ca2+ regulation
- Lungs= RAAS
- Heart= ANP
- Liver= IGF-1/ somatomedin C
- Gut= Leptin, Ghrelin
- Vascular epithelium= endothelin
- Adipose= glucocorticoids
- Skin= stress response hormones
- Salivary glands= growth factors
What is the endocrine axis?
- Hypothalamus + anterior pituitary + endocrine gland + hormone + target tissue
- Hypothalamic releasing hormone= promote release of anterior pituitary hormone= action of distant target gland= target gland response= physiological response
- Hypothalamic- pituitary- target gland axis (thyroid, adrenal, gonad, liver)
Describe homeostasis
-Balance of hormone production and action maintains the internal environment in a balanced state
=hormones released from HP act on target glands to elicit hormone release
=Hormones released from target endocrine glands ‘feedforward’ to target tissues and feedback to inhibit their own production
Describe amplification and degradation of hormones
-Amplification
=’Signalling’ hormones (short half-life only a few mins)
=’End-organ’ hormones (long-lived hours to days)
- Degraded mainly in liver and kidneys (increased in rate in fast metabolism)
- Breakdown products excreted in urine, faeces and bile
What central neural inputs does the hypothalamus coordinate?
-External environment:
=sight, sound, touch, taste, smell, pain, heat, cold , fear (‘freeze, fight or flight’)
-Internal physiology:
=blood pressure, osmolality, blood glucose, hypoglycaemia, starvation chronic pain, fever, inflammation
-Circadian biological clock:
=Suprachiasmatic nucleus (SCN) rhythm generator controls daily endocrine system cycles (entrained by daily light & dark cycle)
Describe the hypothalamus
- Neuroendocrine component of the nervous system within the brain
- Located at the base of the brain
- Linked via the pituitary stalk to the pituitary gland outside the brain
Describe the pituitary gland
-Anterior and posterior pituitary have different embryological origins
-Anterior pituitary:
=blood supply from median eminence
-Posterior pituitary:
=Innervated by hypothalamic axons (extension of CNS)
=oxytocin and vasopressin accumulates
How does the hypothalamus coordinate central neural inputs?
-Stimuli from somatic & visceral sense organs
-Transmitted via sensory & motor neurons from the forebrain and mid brain
-Produce ‘stimulatory’ or ‘inhibitory’ neurotransmitters
=(dopamine, adrenaline, noradrenaline, serotonin, acetylcholine & various neuropeptides)
-Act on distinct hypothalamic ‘nuclei’
=stimulate production of hypothalamic-releasing hormones (peptide synthesis)
What is the median eminence?
- Functional link between the hypothalamus and the anterior pituitary gland.
- On surface of pituitary stalk
- Lies in the centre of the tuber cinereum and is composed of an extensive array of blood vessels and nerve terminals
Describe blood supply to and from the median eminence
- Its extremely rich blood supply arises from the superior hypophyseal artery (a branch of the internal carotid artery), which sends off many small branches that form capillary loops.
- The small capillary loops extend into the internal and external zones of the median eminence, form anastomoses, and drain into sinusoids that become the pituitary portal veins that enter the vascular pool of the pituitary gland.
How is blood supply to the median eminence an advantage?
- The flow of blood in these short loops is predominantly in a hypothalamic-to-pituitary direction.
- This well-developed plexus results in a tremendous increase in the vascular surface area.
- The vessels are fenestrated (no endothelial cells), allowing diffusion of the peptide-releasing factors to their site of action in the anterior pituitary gland.
What is the hypophyseal-portal circulation?
-Because this vascular complex in the base of the hypothalamus and its “arteriolized” venous drainage to the pituitary compose a circulatory system analogous to the portal vein system of the liver, it has been termed the hypophyseal-portal circulation.
What is a portal circulation?
-Two capillary beds joined by a circulation without recycling back into the systemic circulation/ through heart and lungs
What happens when the pituitary stalk is damaged (like in a car crash)?
- Cranial diabetes insipidus
- Deficit of vasopressin as no transport into posterior gland
What are the different cell types in the anterior pituitary gland and what hormones ACT on them?
- Growth Hormone-Releasing Hormone (GHRH) acts on Somatotrophs
- Gonadotrophim-Releasing Hormone (GnRH) acts on Gonadotrophs
- Corticotrophin-Releasing Hormone (CRH) acts on Corticotrophs
- Thyrotropin-Releasing Hormone (TRH) acts on Thyrotrophs
- Dopamine (DA), inhibits Lactotrophs
- Somatostasin (SS) inhibits Somatotrophs & Thyrotrophs
What do the 5 anterior pituitary gland cell types secrete?
- Adrenocorticotrophic hormone (ACTH) from Corticotrophs
- Thyroid-stimulating hormone (TSH) from Thyrotrophs
- Follicle-stimulating hormone (FSH) & Leutenising hormone (LH) from Gonadotrophs
- Growth hormone (GH)/Somatotrophin from Somatotrophs
- Prolactin (PRL) from Lactotrophs
What are the actions of the anterior pituitary gland hormones?
-Growth hormone (GH):
=In children, stimulates growth
In adults, affects muscle mass, bone mass, and fat distribution
-Adrenocorticotrophic hormone (ACTH):
=Stimulates the adrenal glands to release cortisol, which helps maintain blood pressure and blood glucose (sugar) levels, especially during stress, illness, or injury
-Thyroid-stimulating hormone (TSH):
=Stimulates the thyroid gland to make thyroid hormones, which regulate metabolism and energy balance
-Luteinizing hormone (LH):
=Stimulates ovulation in women and testosterone production in men
-Follicle-stimulating hormone (FSH):
=Stimulates oestrogen production and egg development in women and sperm production in men
-Prolactin (PRL):
=Stimulates production of breast milk after childbirth
May affect menstrual periods, sex drive, and fertility
What are the actions of the posterior pituitary gland hormones?
-Antidiuretic hormone (ADH); =Vasopressin (VP)
=Baroreceptors in carotid sinus and aortic arch
=Regulates the amount of water the body releases in the urine
-Oxytocin (OT):
=Helps the flow of breast milk
=Helps with labour during childbirth
‘Feedforward’ response
Describe the homeostatic feedback
- Stimulatory or inhibitory external neural inputs
- Hypothalamic releasing-hormone acts on pituitary
- Anterior pituitary hormone acts on target gland
- Target gland hormone feeds back on Pit & Hyp
- Feeds forward on tissue target/metabolism
How does target gland tumours lead to target gland hormone excess?
Hormone producing tumour results in:
HIGH levels of target gland hormone
increases feedback on hypothalamus & pituitary
leading to:
LOW levels of hypothalamic-releasing & anterior pituitary hormones,
all of which can be measured
How does pituitary tumours lead to pituitary and target gland hormone excess?
Hormone producing tumour results in:
HIGH levels of pituitary gland hormone
leading to:
HIGH levels of target gland hormones,
all of which can be measured
Pituitary tumour is unresponsive to feedback
How does primary end organ failure lead to target gland hormone deficiency?
Failure of target gland results in:
LOW levels of target hormone,
reducing feedback on the hypothalamus & pituitary
leading to:
HIGH levels of hypothalamic releasing and anterior pituitary hormones,
all of which can be measured
How does secondary end organ failure (pituitary failure) lead to multiple anterior pituitary hormone deficiency?
Failure of pituitary results in:
LOW levels of anterior pituitary & target gland hormone, reducing feedback on the hypothalamus
leading to:
HIGH levels of hypothalamic releasing hormones
all of which can be measured
Examples of suppression testing
-Overnight Dexamethasone suppression test
=synthetic glucocorticoid suppresses pituitary ACTH secretion & cortisol production from adrenal cortex (negative feedback)
-Comes in two flavours:
=Low dose: suppresses pituitary ACTH secretion and cortisol production in normal individuals, but not from a pituitary adenoma
=High dose: part-inhibits ACTH secretion from a pituitary adenoma, but not from a cortisol-producing adrenal adenoma or an ectopic ACTH-producing tumour
Examples of Stimulation testing
-SynACTHen (synthetic ACTH) stimulation test:
=quantifies adrenal function or lack of function (insufficiency)
=Comes in two flavours:
==Low dose: to measure cortisol production
==High dose: to assess total adrenal cortex function
-Oral Glucose Tolerance test =Diagnosis of diabetes (exaggerated glucose response)
=Diagnosis of acromegaly (GH fails to be supressed as normal)
What hormones are rarely measured in plasma?
-Hypothalamic hormones =CRF =GnRH =GHRH =TRH =Dopamine
Measured by petrosal sinus sampling
What hormones are often measured in plasma?
-Pituitary hormones =ACTH =LH/FSH (male and female) =GH =TSH =ADH/ vasopressin =Prolactin
What hormones are measured in plasma for diagnosis and to monitor hormone reduction or replacement?
-End Organ hormone =Cortisol =Testosterone =Oestrogen, progesterone =IGF1 (GH in children) =Thyroxine =Desmopressin (DDAVP)
