lecture 1 what is a hormone and the steroid hormones Flashcards
The Endocrine System: Physiological Importance
*Controls many/most aspects of physiology, via secretion of hormones
*Endocrine and neuronal (nervous) systems are considered the 2 major control systems
*However, substantial interaction between them (emergence of ‘neuroendocrinology’ as a discipline)
*Endocrine systems also interact with e.g. the cardiovascular, digestive and immune systems
endocrine and neuronal systems are the major controls of our physiological systems
-hormonal and neuronal systems interact very closely and interact with other systems such as our cardiovascular and digestive systems
Endocrinology in the News!
*Hormones are related to ‘media-friendly’ topics e.g.
–Sex
–Metabolism/appetite
–Body clocks
–Behaviour
–Major diseases (diabetes, cancer etc)
*Endocrine disrupters- Endocrine disruptors (EDCs) are chemicals that can interfere with the body’s hormones and the endocrine system:
What they are-
EDCs can mimic, block, or interfere with hormones. They can be natural or human-made
*Drug treatment
–HRT, oral contraceptives (inc. “male pill”)
–Anabolic steroids/athletics
What is a Hormone?
*The word “hormone” 1st used by Ernest Starling (1905)–whilst working with Duodenal secretion(s) saw that they stimulate pancreatic activity
*Hormones can be grouped by their biochemistry
–Dynamics of secretion and action vary greatly, depending on the hormone and its physiological role
–Steroid hormones and thyroid amines typically have slow/prolonged actions
–Peptides and adrenal amines typically have rapid/short duration actions
–The name of a hormone will often tell you what biochemical group a hormone falls into and therefore enable you to make easy predictions of its effects
Definition
A hormone is a molecule that is produced by endocrine glands and carried in the blood to target cells.
Function
Hormones affect many bodily processes, including growth and development, and metabolism.
How they work
Hormones work by binding to receptors on target cells, which triggers a biochemical reaction that modifies the cell’s function.
Examples
Some examples of hormones include thyroid-stimulating hormone (TSH), growth hormone (GH), anti-diuretic hormone (ADH), and prolactin.
Steroids and thyroid amines
*Lipophilic molecules
–What does ‘lipophilic’ mean?- something that is fat-loving- so relatively soluble in fats and relatively insoluble in water
–lipophilic character means they are capable of diffusing across cell membranes and so can Diffuse passively out of cells that synthesise them- lipophilic nature also means they do not dissolve in the blood
–typically found Bound to carrier proteins in the blood to make them more soluble
–Can diffuse into target cells across the cell membranes and act on intracellular receptors
Intracellular receptors
- hormone binds to a receptor in the cell and these act as transcription factors which either turn on or turn down the transcription rate of many genes
they can affect hundreds or thousands of genes so as a result their actions are very slow, to turn on a gene takes time and then you’ve to get an increase or decrease in the amount of mRNA that is produced which also takes time, then there is a delay in the before you get in a change in the steady state of the mRNA of that gene, then there’s a further delay before you get a change in the protein concentration downstream of that, therefore there’s a further delay before you get a functional change as a result of that hormone action.
–Receptor-hormone complexes act as transcription factors
*Regulate (increase or decrease)
expression of hundreds of target genes
–Effects often have slow onset and prolonged duration
Intracellular Receptors in regard to steroid and thyroid amines
*Mechanism of action for steroids and thyroid hormones
*Regulate gene expression → delayed & prolonged response
- the hormone will increase or decrease the production of mRNA from a gene and that will result in an increase or decrease in the formation of certain proteins
action
1. This orangy colour represents the cell. And the red circular bit represents the nucleus within the target cell.
- This green triangle represents our lipophilic hormone.So our steroid over soluble thymine.
- As it’s lipophilic it diffuses across the cell membrane and gets inside the cell and binds to a receptor. And that receptors are either found within the cytoplasm or within the nucleus.
- And you get this hormone receptor complex. So you get a little combined structure here. The hormone receptor complex is either formed within the nucleus or if it forms in the cytoplasm then passes into the nucleus where it binds to the regulatory components of its genes of um of target and will either increase or decrease the transcription of that gene. So over time you get more or less of the mRNA produced, depending upon the stability of the mRNA. You will then gradually get an increase or decrease in the overall concentration of mRNA within that cell.And then as a result of the change in mRNA, you’ll get a change in protein concentration which then causes a change, in the physiology of that particular cell.
-all of these steps take time
Peptides (protein-based hormones) and adrenal amines
*Usually hydrophilic molecules so dissolve readily in water or aqueous substances
-usually produced, by the cell that wants to secrete them, and they are stored in vesicles within the cytoplasm of that cell.
–Stored in vesicles and secreted by exocytosis
- When the cell receives a signal to secrete that hormone, the hormones are secreted by the process of exocytosis
–they are hydrophilic so Dissolve readily in blood plasma, so they don’t need carrier proteins to get them around the blood.
–however also means they Cannot easily get inside target cells as a result of being easily dissolved in blood plasma and so act on plasma membrane receptors
*Plasma membrane receptors
–Have rapid onset of action, e.g. regulating ion channel opening or directly linked to a key signalling enzyme
–Effects are often short-lived
Membrane-Bound Receptors
*Mechanism of action for hydrophilic peptide and amine hormones
*Proteins present in the plasma membrane
*Many different types, but all have 3 basic domains
–Extracellular (binds hormone)
–Transmembrane- this is the bit that the hormone will bind to, there will be a very specific three dimensional binding pocket in the extracellular part of the receptor to which the hormone very specifically combines, when it binds to that, it causes a three dimensional change in the structure of that receptor, that three dimensional change will cause an activation of this intracellular part down in the cytoplasm
–Intracellular (often necessary for effects in target cell, e.g. change in enzyme activity, the intercellular part will be coupled to some kind of signal transduction process within the cell that causes the cellular response.
- there are lots of different types of signal transduction pathways that these receptors can work through.
- In some cases, the change in the receptor structure actually causes a direct opening of an ion channel, and so ions can very quickly flood in or out of the cell according to their concentration gradient.
-sometimes the intracellular part of the receptor is coupled to an enzyme, and when the hormone binds to the receptor, it causes a very rapid activation of that enzyme, which then signals various processes within the cell.
So an example of a hormone that causes a rapid change in ion channels would be adrenaline and one That causes a change in enzyme activity would be insulin.
Typically, responses are rapid,
- change in membrane permeability(e.g. adrenaline)
-change in enzyme activity(e.g. insulin
If you understand this, you will understand why the peptide hormones and adrenal amines have a very rapid onset of action. Because these changes in the receptor structure occur almost instantaneously after the hormone is bound to them.
Major Endocrine Organs
*Hypothalamus
Releasing hormones: GHRH, CRH, TRH, GnRH,
vasopressin
Inhibitory hormones: somatostatin, dopamine
*Pituitary gland
Growth hormone
Prolactin
ACTH, MSH
TSH FSH and LH
*Thyroid gland
Thyroid hormones and Calcitonin
*Parathyroid glands
Parathyroid hormone
*Adrenal glands
Adrenal cortex:
Cortisol
Aldosterone
Adrenal androgens
Adrenal medulla:
Epinephrine
Norepinephrine
*Pancreas
insulin
glucagon
*Testes
testosterone
*Ovaries
estrogen
progesterone
Other Important Endocrine Organs
*Pineal gland–secretes melatonin–important for biological rhythms, sits in the brian
*Adipose tissue (fat) & Gastrointestinal tract–secrete many hormones involved in energy balance & metabolism, it is also an important metabolic store for lipids
*Placenta–secretes hormones involved
in foetal and maternal development, transports nutrients and waste products between the foetus and the mother
almost every single tissue in our body forms hormones
Feedback Loops
Negative
*Imposes “brake” on system
*Important for homeostasis
*Common in physiology(inc. endocrinology)
-target cell will have a physiological response in response to the hormone and signal back to the endocrine cell the increasing response of the target cell and so the endocrine cell will reduce the amount of hormone produced; this is imposing some kind of brake on the system, regulating its activity and balance; this is called homeostasis- negative feedback is the main mechanism to maintain homeostasis
Positive
- opposite of homestasis
*Amplifies original signal
*By itself, not compatible with homeostasis
*Requires additional control mechanism(s)
-positive feedback is only found in these highly specific cases where the body needs a very quick, almost instantaneous rise in the activity of a system however once this physiological function that’s caused and stimulated by the positive feedback is happened, there will always be a cut off mechanism that stops the positive feedback loop and enables our bodies to go back into negative feedback and and homeostasis.
Negative Feedback Loops:Hypothalamo-Pituitary Regulation
General Model (anterior pituitary loops)
Hypothalamus –releasing hormone–> Pituitary–trophic hormone–> target Gland–target gand hormone–>back up to pituitary or hypothalamus
Cortisol Secretion
Hypothalamus–cortincotrophin releasing hormone (BRH)–> Pituitary–adrenocorticotrophin hormone (ACTH)–> Target Gland–Cortisol–> back to pituitary (via adrenal cortex)–> back to hypothalamus (via corticotroph cells)
True or false. Some hormones may require hours to days to exert their full physiological effect
Some hormones, especially those that regulate gene expression, such as steroid hormones (e.g., cortisol, estrogen, testosterone) and thyroid hormones, may take hours to days to exert their full physiological effects. This is because they often need to enter the cell, bind to intracellular receptors, and initiate changes in gene transcription and protein synthesis, which are slower processes.
In contrast, other hormones like peptide hormones (e.g., insulin, glucagon) can have much faster effects, often within minutes, as they work through membrane receptors and second messenger systems.
Consider the negative feedback loop regulating cortisol secretion (slide 14). What would be the effect of removal of ACTH on the secretion of (a) cortisol and (b) CRH?
In the negative feedback loop regulating cortisol secretion, ACTH (adrenocorticotropic hormone) plays a critical role in stimulating the adrenal glands to produce cortisol. Removal of ACTH would disrupt this regulation. Here’s what would happen:
(a) Effect on Cortisol Secretion:
-Cortisol secretion would decrease. ACTH stimulates the adrenal cortex (target gland) to produce cortisol. If ACTH is removed, cortisol production would significantly drop because there is no signal to activate its synthesis and release.
(b) Effect on CRH Secretion:
-CRH (Corticotropin-releasing hormone) secretion would increase. In the absence of ACTH, cortisol levels would drop. Low cortisol levels would remove the negative feedback inhibition on the hypothalamus and the pituitary gland. As a result, the hypothalamus would secrete more CRH to try to stimulate the pituitary to release more ACTH.
Summary:
-Removal of ACTH would reduce cortisol secretion.
-The drop in cortisol would trigger an increase in CRH secretion due to loss of negative feedback.
What best describes the role of negative feedback loops?
Negative feedback loops help maintain homeostasis by regulating physiological processes and keeping them within a narrow, stable range. Here’s what best describes their role:
(c) maintains homeostasis
Role of Negative Feedback Loops:
-Stabilization of Physiological Systems: Negative feedback loops counteract changes in the body to bring a physiological variable back to its set point. When a deviation occurs (e.g., an increase or decrease in a certain hormone or condition), the feedback mechanism works to reverse that change.
-Prevention of Overreaction: They prevent excessive responses by reducing the output or activity once the desired effect is achieved, ensuring that the system does not go beyond optimal levels.
Examples:
-Endocrine system: For instance, high levels of cortisol inhibit the release of ACTH and CRH, reducing further cortisol production.
-Temperature regulation: When body temperature rises, mechanisms such as sweating are triggered to cool the body down.
Summary:
Negative feedback loops are crucial for maintaining balance in biological systems by reversing deviations from a set point, stabilizing internal conditions, and preventing overproduction or excessive responses.
