NEURO: Neurohormones Flashcards
Describe neurohormones.
Neurohormones are produced by specialised nerve cells called neurosecretory cells and are released into the blood. Because they are defined as hormones, they are secreted into the blood and have their effect on cells some distance away. The same compounds can also act as neurotransmitters or as autocrine (self) or paracrine (local) messengers.
Describe the two main control systems of the body (compare and contrast).
The body has two main control system: the endocrine system and the nervous system.
ENDOCRINE SYSTEM:
- mediators travel within blood vessels
- utilises chemical mediators (hormones)
- slow communication
- effects can be long-lasting
NERVOUS SYSTEM:
- signalling along the nerve fibres
- transmission of electrical impulses
- fast communication
- effects are generally short-acting
Describe the different types of hormones.
PROTEIN & PEPTIDE HORMONES:
- vary considerably in size
- can be synthesised as a large precursor and processed prior to secretion (eg. GH, somatostatin, insulin)
- can be post-translationally modified (eg. glycosylation)
- can have multiple subunits synthesised independently and assembled (eg. FSH, LH, TSH)
AMINO ACID DERIVATIVES:
- mostly tyrosine-derived
- neurotransmitter that can also act as a hormone
- eg. epinephrine, norepinephrine, dopamine
STEROID HORMONES:
- steroids are a class of lipids derived from cholesterol
- includes cortisol, aldosterone, testosterone, progesterone, oestradiol
Describe endocrine rhythms. (SS Flashcards)
Most, if not all, bodily activities show periodic rhythms or cyclic changes. Many of the hormones show periodicity.
CIRCADIAN RHYTHMS: based on a 24-hour cycle (eg. secretion of cortisol, GH, PRL)
PULSATILE (ULTRADIAN) RHYTHMS: periodicity of fewer than 24 hours (usually every 1/2 to 2 hours) (eg. secretion of gonadotrophin in adults)
INFRADIAN RHYTHMS: periodicity of longer than 24 hours (eg. menstrual cycle)
List some of the principal endocrine organs in the body.
The hypothalamus and pituitary are packed with neurohormones.
- Hypothalamus: TRH, GnRH, CRH, GRHR, Prolactin-inhibiting factor (dopamine), somatostatin
- Pituitary gland:
Anterior - TSH, LH, FSH, GH, Prolactin, ACTH
Posterior - Vasopressin, Oxytocin - Thyroid gland: Thyroxine, Triiodothyronine, Calcitonin
- Parathyroid glands: Parathyroid hormone
- Adrenal gland:
- Adrenal Cortex –> Aldosterone, Cortisol
- Adrenal Medulla –> Adrenaline, Noradrenaline
- Pancreas: Insulin, Glucagon, Somatostatin
- Ovary (females): Oestrogens, Progesterone
- Testes (males): Testosterone
What are the 4 patterns of communication in the nervous system?
- Neurotransmission (point to point communication) - fast, restricted (action potentials)
- Neuroendocrine system (neurons of secretory hypothalamus) - slow but widespread (neurons secrete hormones directly into the blood)
- Networks of interconnected neurons - Autonomic Nervous System - fast, widespread influence
- Diffuse modulatory systems - slower, widespread
Neuropeptides (neurohormones) are functionally important transmitters in the Hypothalamo-pituitary axis. Describe the anatomy of the hypothalamo-hypophyseal system.
The HPA has 2 components (anterior and posterior pituitary).
How are hormone signals sent to both parts of the pituitary?
With the anterior pituitary, we have the hypophyseal portal circulation. Neurosecretory cells produce releasing and release-inhibiting hormones in the hypothalamic neurons. Hormones are released into these blood vessels (portal system), which transport them to the anterior pituitary, where they activate specialised cells leading to the release of neurohormones (ACTH, LH, TSH etc). Each type of hypothalamic neurohormone either stimulates or inhibits production and secretion of an anterior pituitary hormone.
With the posterior pituitary, we have neurones called magnocellular neurons, which project from the hypothalamus (the paraventricular nucleus and superoptic nucleus) which produce and secrete oxytocin and vasopresin directly into the posterior pituitary. The hormones travel through the capillary network and get released straight into the blood circulation. So the hormones are synthesised in the hypothalamus and secreted from the posterior pituitary gland.
List the hormones that control the pituitary, and what effect they have.
ANTERIOR PITUITARY:
- corticotrophin releasing hormone (CRH):
a peptide that controls the release of adrenocorticotrophin (ACTH) to act on the adrenal cortex to release cortisol
- thyrotrophin releasing hormone (TRH):
a peptide that controls the release of thryoid stimulating hormone (TSH) which act on the thyroids to release thryroid hormone (TH) and prolactin (PRL) - gonadotrophin releasing hormone (GnRH):
a peptide that controls the release of luteinising hormone (LH) and follicle-stimulating hormone (FSH) to act on testis/ovaries. - growth hormone releasing hormone (GHRH):
a peptide that controls the release of growth hormone (GH) to act on bones/muscles. - growth hormone inhibitin hormone (somatostatin):
a petide that inhibits the release of GH, gastrin vasoactive intestinal polypeptide (VIP), glucagon, insulin, TSH and PRL - dopamine (DA):
a monoamine that inhibits the release of PRL which acts on the mammary glands.
POSTERIOR PITUITARY:
The posterior pituitary releases vasopressin (which has an antidiuretic effect by acting on the kidney and also increases blood pressure through vasoconstriction) and oxytocin (which acts on the uterus to induce uterine contraction, and acts on the mammary glands to induce milk ejection).
List the specialised cells of the anterior pituitary and what they release.
The anterior pituitary contains specialised cells responding to these hypothalamic hormones:
GONADOTROPH cells that secrete LH and FSH in response to GnRH.
SOMATOTROPHS that control GH secretion in response to GHRH.
CORTICOTROPHS that control ACTH secretion in response to CRH.
THYROTROPHS that regulate TSH secretion in response to TRH.
LACTOTROPHS that control the secretion of prolactin in response to TRH, somatostatin and dopamine.
Describe the effects of stress and the role of ACTH in the release of cortisol.
In response to stress, 2 pathways are activated. There is the release of noradrenaline leading to arousal and sympathetic activation, and there is also the activation of the hypothalamic pituitary axis.
Stress will cause the hypothalamic neurones release corticotrophin-releasing hormone (CRH) to stimulate the anterior pituitary corticotrophs to release ACTH into the circulation.
ACTH stimulates the production of glucocorticoid (cortisol) and sex hormone from the zona fasciculata of the adrenal cortex.
Cortisol provides negative feedback to the hypothalamus and pituitary, reducing the amount of CRH and ACTH released.
Cortisol is regulated by negative feedback loops acting on the pituitary (decrease ACTH release) and hypothalamus (decrease CRH release).
ACTH belongs to a family of peptide hormones derived from a large precursor glycoprotein, pro-opiomelanocortin (POMC). Cortisol is a steroid hormone, more specifically a glucocorticoid. Hydrocortisone is a name for cortisol used in medication.
Describe glucocorticoid secretion through the day
Following changes in brain activity, plasma cortisol levels are highest first thing in the morning and decline during the day (reflecting the pattern of ACTH secretion by the anterior pituitary). This circadian rhythm must be taken into account when considering cortisol replacement therapy as a clinical treatment. The pattern of cortisol secretion probably reflects the body’s response to low blood glucose after overnight fasting. It is important to test for glucocorticoid levels at the same time.
Describe the regulation of TSH and thyroid secretion by negative feedback.
Thyrotropic releasing hormone (TRH) from the hypothalamus stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH).
TSH acts on the thyroid to increase T3/T4 secretion, T3 is the most potent thyroid hormone, and targets the tissues containing a deiodinase enzyme (DI) to convert T4 to T3.
The pituitary also expresses deiodinase to convert T4 to T3 to facilitate negative feedback. The negative feedback loop affects the hypothalamus (inhibit TRH secretion) and pituitary (inhibit TSH secretion).
Thyroxine increases basal metabolic rate and can lead to weightloss. Too high thyroxine levels can cause hyperthyroidism, tachycardia, anxiety, etc. On the other hand too little thyroxine, it can lead to weight gain, low energy, cognitive impairment, etc.
Describe the action of prolactin and its regulation.
It is released by the lactotrophs in the anterior pituitary.
It stimulates mammary gland development during puberty. It also maintains lactation (synergised by glucocorticoids, inhibited by oestrogen and progesterone - we get a decrease in both after parturition).
It sregulation is under the dominant negative control of dopamine. It’s increased during pregnancy and lactation.
Describe the synthesis and transport of the hypothalamic neurohormones that regulate the posterior pituitary.
The neurohormones of the posterior pituitary are vasopressin and oxytocin.
They are synthesised in the supraoptic and paraventricular nuclei in the hypothalamus.
They’re transported to the terminals of the nerve fibres located in the posterior pituitary.
Structurally, they’re quite similar (only a 2 amino acid difference in a 9 amino acid structure), yet they have very different functions.
Describe the peripheral effect of oxytocin during labour.
When it is ready for birth, the foetus pushes on the walls of the uterus (stretching it), causing various neurons in the uterus to project to the hypothalamus and activate the magnocellular neurons leading to the release of oxytocin.
This stimulates uterine contractions. It also stimulates the release of more oxytocin (positive feedback) and only stops when the baby have been delivered.
The mechanism of action of the neurohormones at the cellular level depends on the classes of the hormones and their receptors.
Describe the mechanism of action of peptide/protein hormones (eg. GH).
Peptide and protein hormones bind to surface receptors and activate intracellular signalling mechanisms that result in alteration of target protein and/or enzyme activities.
Binding of insulin and growth hormone to its cell surface receptors leads to the dimerisation of the receptors, subsequently recruiting tyrosine kinases (e.g. JAK2 or MAPK) which phosphorylate a target protein (e.g. STAT) to induce a biological response.
Mutations in the G receptor gene can result in defective hormone binding or reduced efficiency of receptor dimerisation (e.g. GH resistance = “Laron Syndrome”).
The mechanism of action of the neurohormones at the cellular level depends on the classes of the hormones and their receptors.
Describe the mechanism of action of TSH and ACTH.
Binding of hormones to GPCRs results in conformational changes in the receptor, leading to GTP exchange for GDP and catalytic activation of adenylate cyclase.
TSH and ACTH bind to cell surface GPCRs and activate G-proteins that stimulate or inhibit adenylate cyclase. Stimulation of adenylate cyclase increases intracellular cAMP levels that activate protein kinase A. This phosphorylates target proteins (eg. CREB) to initiate specific gene expressions and biological responses.
Activating mutations of the TSH receptor can lead to thyroid adenomas (constitutively on).
Inactivating mutations of the TSH receptor can lead to resistance to TSH.
The mechanism of action of the neurohormones at the cellular level depends on the classes of the hormones and their receptors.
Describe the mechanism of action of oxytocin and GnRH.
DAG/IP3 PATHWAY:
Oxytocin and GnRH bind to cell surface GPCRs (Gq coupled) and stimulate phospholipase C. It converts phosphatidylinositol biphosphate (PIP2) into inositol triphosphate (IP3) and diaglycerol (DAG).
IP3 stimulates Ca2+ release from intracellular stores, particularly the endoplasmic reticulum. DAG activates PKC. These stimulate the phosphorylation of proteins and alter enzyme activities to initiate a biological response.
Loss-of-function mutations in GnRHR can lead to sex hormone deficiencies and delayed puberty (hypogonadotrophic hypogonadism).
The mechanism of action of the neurohormones at the cellular level depends on the classes of the hormones and their receptors.
Describe the mechanism of action of cytoplasmic/nuclear receptors.
Cytoplasmic/nuclear receptors:
Steroid and thyroid hormones can diffuse across the plasma membrane of target cells and bind to intracellular receptors in the cytoplasm or the nucleus.
These receptors function as hormone-regulated transcription factors, controlling gene expression. Nuclear receptors commonly share a transcriptional activation domain (AF1), a Zn2+ finger DNA binding domain and a ligand (hormone) binding/dimerisation domain.
There are over 150 members of receptor proteins, majority of which are ‘orphan’ receptors.
