The hypothalamus-pituitary axis - Part 1 Flashcards
What are the Major Endocrine Glands and their features?
Endocrine features;
- Endocrine glands are ductless (lacks ducts)
- Some are discrete organs (pituitary, adrenals, thyroid, etc)
- Others associated with other tissues (e.g pancreas)
- Others scattered within complex organs (ovary, testes, GI)
- Many have complex embryological origins
- Gland/cell characteristics reflect types of hormone secretions
Endocrine Glands;
- Hypothalamus + Pituitary
- Thyroid and parathyroids
- Adrenals (cortex and medulla)
- Stomach and gut
- Pancreas
- Ovaries
- Tesies
What are endocrine glands Mode of Secretion?
- Endocrine glands are very vascular (menstruated capillaries - don’t have ducts)
- Some hormones diffuse directly into capillaries to act on distant target organs (classic endocrine secretion)
- Others are secreted and act more locally (paracrine secretion)
- Some hormones act directly on the cell that produces it (autocrine secretion) - Feedback loop with itself suppressing further release
What are the different classes of hormones we have and why ?
Many endocrine glands have complex embryological origins
Gland / cell characteristics reflect types of hormone secretions
Steroids;
- diffuse into cells and alter gene expression, slow onset long duration
- Oestrogens, androgens (testosterone), progesterone, cortisol, aldosterone
Peptides;
- short chain amino acids chained together- synthesised as prohormones that have to be processes to be activated. Rapid onset, some can effect gene expression
- Thyrotropin-releasing hormone (TRH), Gonadotropin-releasing hormone (GnRH), Oxytocin (OT), Vasopresin, Vasoactive intestinal peptide (VIP), Glucagon, Adrenocorticotropic hormone (ACTH), Somatostatin
Protein hormone;
- larger peptide hormone, multiple chains, increased complexity
- Insulin, Insulin-like growth factors (IGF), Prolactin (PRL), Growth Hormone (GH), Placental lactose (PL), Parathyroid hormone (PTH)
Glycoproteins;
- sugar parts added to amino acids
- Thyroid-stimulating hormone (TSH)
- Follicle-stimulating hormone (FSH)
- Luteinising hormone (LH)
- Chorionic gonadotropin (CG)
Amino acid;
- thyroid hormones (T3 + T4) and Epinephrine (adrenaline)
Learning Outcome: Explain the general types of hormones and modes of secretion - don’t know all of this just types and a few
What are the 3 ways to control the release of hormones?
Humoral;
- Capillary blood contains low concentration of Ca2+ which stimulates secretion of the parathyroid hormone (PTH) by the parathyroid gland
Neural;
- Preganglionic SNS fibre stimulates adrenal medulla cells to secrete Catecholamines (like norepinephrine)
Hormonal;
- The hypothalamus secretes hormones that stimulate the anterior pituitary gland to secrete hormones that stimulate other endocrine glands to secrete hormones (e.g Thyroid gland, adrenal cortex, Gonad / Testis)
How does Negative Feedback play a role in hormone regulation and give an example of this going wrong?
- Feedback mechanisms protect the body from hormone excess
- Negative feedback is fundamental for homeostatic mechanisms
- T3 (and a lesser degree T4) in the hypothalamic-pituitary-thyroid axis exerts feedback inhibition on the other elements higher up in the axis
What patterns of hormone recognition do we see in different hormones, label this graph?
1). Diurnal innervation - Hormone A - Some hormones are under diurnal innervation making them have a predicatble change and hormone pattern over 24 hours, controlled by part of brain that is a pacemaker and releases at certain times day, will peak certain time during day and drop and build up during night and peaks in morning - hormone A e.g cortisol
2). Set Point regulation - Hormone B - e.g - T4
3). Episodic - Hormone C - Some hormones are released in response to stimulus (e.g high blood sugar then insulin produced). Insulin fluctuates throughout day in response to blood glucose level
- Before a meal or fasting insulin level is almost undetectable
Where is the Hypothalamus and Pituitary located?
The Hypothalamus and Pituitary lie immediately posterior to the optic chiasma and sphenoid sinus
What are Neurohormones?
Large degree of interaction of nervous system and endocrine.
Several hormones that are released from neurons in the hypothalamus, that respond to action potentials in the same way that neurotransmitters are released, called neurohormones (made by neurons in brain, act like hormones).
- Release in blood and travel to target tissues (hypothalamus, posterior pituitary adrenal medulla)
How does the Hypothalamus and Pituitary interact and what hormones are produced where?
Some neurons project all the way down sending their nerve endings to posterior pituitary (to release oxytocin and vasopressin) and enter the general circulation. (Neurohypophysis = secrets 2 hormones produced in hypothalamus)
Anterior pituitary is separate, and release hormones in medial eminence or primary plexus (blood system that is connecting to the anterior pituitary).
Anterior pituitary has lots of hormone producing cells, so this is a way the hypothalamus controls the anterior pituitary by secreting hormones into the vasculature which gets transported through blood into target cells in anterior pituitary (adenohypophsis = produces and secrets own hormones)
What Neurohormones control the anterior pituitary hormones?
- Prolactin releasing hormone (PRH)
- Prolacting-inhibiting hormone (PIH produces Dopamine)
- Thyrotropin-releasing hormone (TRH; modified amino acid peptide)
- Corticotropin-releasing hormone (CRH; 41 amino acid peptide)
- Growth hormone-releasing hormone (GHRH; 42 amino acid polypeptide)
- Somatostatin (SS; cyclic 14 amino acid peptide)
- Gonadotropin-releasing hormone (GnRH; 10 amino acid peptide)
What are the main Nuclei of the Hypothalamus and what do they produce?
Nuclei of the Hypothalamus;
- Paraventriclular Nucelus (CRH, TRH, P.P - OXT, AVP)
Paraventricular - CRasH, ThRougH, Public Places
- Preoptic Nucleus (GnRH)
- Supraoptic Nucleus (P.P - OXT, AVP)
- Arcuate Nucelus (GHRH, PIH)
Arcuate - Grows Hormone Releasing Hormone and PIneapples
What Neurohormones are released from the posterior pituitary ?
- Oxytocin (OXT; 9 amino acid peptide)
- Vasopressin (AVP) (ADH; 9 amino acid peptide)
OX(t)’s have ADHd in Posterior Pituitary
How does the Hypothalamic-pituitary Endocrine physiology work?
Magnocellular / Large-bodied neurons make Vasopressin (AVP) and Oxytocin (OX) and transport these hormones down their axons to the posterior pituitary for release (Posterior Pituitary)
Small-bodied neurons make releasing hormones, transport these down their axons and secrete them into primary capillary plexuses. (Anterior Pituitary)
Where is CRH made and what is its effect on the Anterior Pituitary?
- Corticotropin-releasing hormone (CRH; 41 amino acid peptide)
- Made in Paraventricular Nucleus
- Stimulates ACTH release
Where is TRH made and what is its effect on the Anterior Pituitary?
- Thyrotropin-releasing hormone (TRH; modified amino acid peptide)
- Made in Paraventricular Nucleus
- Stimulates TSH release
Where is GHRH made and what is its effect on the Anterior Pituitary?
- Growth hormone-releasing hormone (GHRH; 42 amino acid polypeptide)
- Made in Arcuate Nucleus
- Stimulates GH release
Where is SS / GHIH made and what is its effect on the Anterior Pituitary?
- Somatostatin / Growth Hormone Inhibiting Hormone (SS; cyclic 14 amino acid peptide)
- Made in Periventricular Nucleus
- Inhibits GH release
Where is GnRH made and what is its effect on the Anterior Pituitary?
- Gonadotropin-releasing hormone (GnRH; 10 amino acid peptide)
- Made in Preoptic Nucleus
- Stimulates FSH + LH release
Where is PRH made and what is its effect on the Anterior Pituitary?
- Prolactin releasing hormone (PRH)
- Don’t know where its made?!?
- Stimulates Prolactin release
Where is PIH made and what is its effect on the Anterior Pituitary?
- Prolacting-inhibiting hormone (PIH produces Dopamine)
- Made in Arcuate + Periventricular Nucleus
- Inhibits Prolactin release
Where is OXT made and what is its effect on the Anterior Pituitary?
- Made in Supraoptic + Paraventricular Nucleus
Where is AVP made and what is its effect on the Anterior Pituitary?
- Made in Supraoptic + Paraventricular Nucleus
How is Vasopressin (AVP) / Anti-Diruetic hormone (ADH) and Oxytocin (OXT) processed in the hypothalamus?
AVP is initially synthesised as the precursor protein Pre-pro-vasopressin, the leading signal/end terminal of that protein has a ‘signal peptide’ which directs the growing protein into the proper routing into the secretory vesicles.
Signal peptide is recognised by certain proteins in the endoplasmic reticulum, they bind to the signal peptide and direct the growing protein into the endoplasmic reticulum for correct routing into the secretory vesicle pathway.
Once in the ER the ‘signal peptide’ is quickly cleaved off and once in the secretory vesicles you get further processing of that hormone (vasopressin), you only get active vasopressin once its been processed with very specific enzymes in the secretory vesicles
Vasopressin the pre-hormone also encodes 2 other proteins, Neurophysin II (carry protein for vasopressin, helps to stabilise and protect AVP and prolong its half life in circulation) and Copeptin (no known function but used as surrogate marker to measure AVP in blood) .
Structures similar with oxytocin, because derived from same ancestorial gene that then evolved. Resultant proteins very similar. Has neurophysin 1 (helps stabilise and prolong life of oxytocin) and no Copeptin
Neurpphysiin circulates with hormone for protection and once near target tissue dissociates and oxytocin and vasopeecin can bind to receptor and do its actions
How is Oxytocin made?
Oxytocin;
- Produced by hypothalamic neurons in the paraventricular and supraoptic nuclei
- Bound by Neurophysin I, stored in secretory granules and carried in the axons to the posterior pituitary
- Release is controlled directly by nervous impulses from the hypothalamus
What event does Oxytocin play a big role in?
Key in childbirth, signals contractions in womb for labour
As foetus grows stretch receptors stimulate neural afferents which feedback to the brain through the medial forebrain bundle, once they surpass a certain threshold these cause biphasic depolarisations of those oxytocin magnocellular neurons, triggering the release of oxytocin from the posterior pituitary, oxytocin then stimulates uterine and uterine muscles and myometrial cells to contract and this helps to educe labour and expel foetus at birth
Synthetic oxytocin can be used to speed up labour process if taking too long
Also plays a role in milk production and ejection
How does Oxytocin and Prolactin help in milk production and ejection ?
- A stimulus from suckling travels from breast, through spinal cord to hypothalamus
- Neurons from the spinal cord inhibit dopamine (DA) release from the arcuate nucelus. The decreased level of Da removes the inhibition that DA normally produces on lactotrophs in the anterior pituitary, leading to prolactin release. Prolactin stimulates milk production
- Neurons from the spinal cord also stimulate the production and release of oxytocin from paraventricular and supraoptic nuclei. Oxytocin is released in the posterior pituitary and into the systemic blood where it makes its way to the breast and myoepithelial cells
- Neurons from the spinal cord inhibit neurons in the acute nucelus and prep-tic area of the hypothalamus, causing a fall in GnRH production. The reduced stimulation of gonadotrophs inhibits the ovarian cycle.
