Lecture 4 Flashcards
The Pancreas
Exocrine - secretes digestive enzymes into the digestive system
Endocrine: Islets of Langerhans Insulin, glucagon, somatostatin and pancreatic polypeptides
Glucose regulation in the blood
Insulin is released after a meal, before food has even reached the digestive system
Takes glucose out of the blood as fat/glycogen in the liver or into muscles
As blood glucose levels drop, glucagon reverses this
Blood glucose levels are very carefully controlled to avoid death
Diabetes Mellitus
Type 1 - autoimmune destruction of B cells
No insulin
Need exogenous insulin
Type 2 - little or insufficient production, insulin resistance
Usually cos ppl ate too much food (environmental)
Thyroid axis
Tyrodotropin releasing hormone (HYP) - thyroid stimulating hormones’ (PIT) - T3 & T4
Both made from iodine
Debate about T4, is it just a prohormone?
Important for metabolism, CNS development, sexual maturation, temp regulation
Thyroid mediated pathology
Cretinism
Low thyroid hormones during prenatal development
Developmental difficulties - low cognitive ability
Hypothyroidism in adults
Rare now - well treated
Increased fatigue, facial puffiness, skin discoloration and dryness
No secondary sexual development
Graves: autoimmune reaction to the receptor for Thyroid Hormones. Blocks it. Therefore no negative feedback. Hence large overproduction of TH.
Bulging eyes
Goiter
Iodine deficiency No TH made Lots of TSH made thyroid enlarges goiter Huge thyroid, low levels of TH
Adrenal axis / The adrenal glands
On kidneys
CRH - ACTH (PIT) - cortisol and adrenalin
Adrenal CORtex (cortisol, aldosterone, androgens, estrogens)
Adrenal Medulla (adrenaline, noradrenaline, dopamine, enkephalins)
Adrenal insufficiency
Waterhouse-fredrichsen - infection
Addison’s autoimmune destruction
Weakness, fatigues, nausea, weight loss, low BP
(baseline levels needed for alertness
Adrenal excess
Cushing’s - often an adenoma
Obesity, high BP
There is some adrenal activity even with no hypothalamic imput.
Without adrenals, the hypothalamus responds to threat with ACTH
Adrenal atrophy is avoided only when a transplanted pituitary is under a hypothalamus (cos it its mechanism)
The gonads
GNRH (HYP) - LH = FSH (PIT) - estrogens, progesterone’s and androgens
Different ratios in men and women
Manufacture (or mature) gametes - FSH control
Manufacture of gonadal hormones is under LH control
Development of secondary sex characteristics at puberty
Both sexes produce all hormones in different ratios
Ovaries
What does LH act on and cause?
What is the follicular phase and what causes it?
What is/causes ovulation?
What is/causes the luteal phase?
LH acts at the Cortical layer - makes ovarian hormones (estrogens, androgens). Contributes to the menstrual cycle
FSH is secreted in greatest amount in the first half of the menstrual cycle, and LH has its peak of secretion at mid-cycle. It is believed that the sequential action of FSH and LH causes ripening of the follicle
Follicular phase - maturation of the follicles, estrogen does this.
Once a level is reached, this estrogen level acts via positive feedback to make a surge of LH and FSH. This surge causes ovulation
Luteal phase: a ruptured follicle becomes the corpus luteum
- Progesterone is produced
- If no fertilization, nothing to continue, hormone levels fall, menses occur.
Male testes
In scrotum for protection and temp maintenance
Leydig cells make hormones under LH control
Test, DHT, estradiol, progesterone
Seminiferous tubules make sperm - FSH control (but needs test too)
Experiments to show how the brain controlled the pituitary - Higgins
It was recognized that the pituitary made substances but not how it was controlled.
A brain region, the hypothalamus, was suspected as it was dorsal to it immediately
Started trying to work out what the hypothalamus would be doing if this were so:
Used menstruations of rabbits as a way to test it. He developed a surgical technique that allowed him to implant electrodes in the rabbits without the need for hormone obscuring anesthesia. He could then electrically stimulate either the hypothalamus or the pituitary (both parts).
Stimulation of hypothalamus leads to ovulation.
Stimulation of the posterior pituitary there is activity
Stimulation of the anterior pituitary yields nothing
As the CNS works by way of electrochemical signaling, this meant that the anterior pituitary was not a part of the CNS, so how does it work?
Did dissections and noted a vascular network around the anterior pituitary. This connects to the anterior pituitary at the median eminence (turns out is a spot where the BBB is permeable). This was conserved in many species, suggesting it was important.
-First the cut this and checked it would heal
-Then they noted that when cut, even with current to the hypothalamus, there is no ovulation
-As the vasculature healed, ovulation was restored.
-If you cut this and block it with wax paper plates then wait until it heals, you still see no ovulation
This showed that the area was important for ovulation but not that is was a substance circulating from the hypothalamus as this could have been accounted for by the pituitary damage.
- transplanted the pituitary to another region
- it embedded itself
- no ovulation
- put it back below the hypothalamus
- ovulation
Hence the vasculature is essential and only functions if it is directly under the hypothalamus therefore something must be passing to the pituitary from the hypothalamus to account for this.
Harris’ work with other hormones
This same technique worked to investigate the affects of many other hormones in the anterior pituitary
HOWEVER, this failed with milk production
Breast feeding
When he cut through the posterior pituitary stalk, there was no milk release
Milk was made (under the control of the anterior pituitary and prolactin) but not released as this requires oxytocin)
However, direct electrical stimulation caused milk release
Hence showing that there are two pathways by which the hypothalamus controls the pituitary gland. The anterior by way of chemical release into the hypothalamic portal circulation and the posterior via neural stimulation.
Harris’ experiment to work out what causes sexual behavior
Hypothalamus/no ovary
What is the mechanism?
Moved to the institute of Psychiatry at the university of London and started to study behavior.
Female rodents do fertile behavior when estrogens peak
Causes ovulation
If you remove the ovaries, you eliminate both fertility and behavior
BUT if you then implant estrogens into the hypothalamus, you get behavior without fertility!
This is because the hypothalamus makes the pituitary secrete chemicals which cause ovulation in the ovaries but the ovaries make hormones that cause they hypothalamus to do appropriate behavior.
How does light affect ferrets breeding (Harris)?
What happens if you block the hypothalamus?
Does it come from the hypothalamus or the pituitary?
Used ferrets as they do not breed in winter
Thought day length might be responsible
His idea was that in summer, longer light caused an increase in gonadal hormones.
EXP1
Put ferrets in the lab, vary the hours of light they receive, observe behavior
Sexual behavior in ferrets with long light only
If you block the portal, you eliminate the effects so he knew the hypothalamus was involved
More light increases activity in the hypothalamus which activates the pituitary which activates the ovaries more which influences behavior… must be via the brain and so there must be a chemical released which acts on this.
How did Harris decide whether sexual differentiation was located in the CNS or Pituitary?
EXP1
Take 4 ferrets
(A) A female with ovaries
(B) A castrated male (no balls)
(C) Androgen sterilized female
(D) Male with testes
Implant an ovary in each and electrically stimulate the hypothalamus
(A) ovulation
(B) ovulation
(C) & (D) no ovulation
Animals who have experienced testosterone in their developmental period (androgenized) with implanted ovaries, will not show ovulation. With no test, males and females will ovulate if they have an ovary.
EXP2
This time transplanted pituitaries and ovaries to animals with both masculinized and unmasculinized hypothalamuses. The hypothalamuses that were not masculinized casued ovulation. The masculinised one’s did not.
This happened irrespective of the developmental origigin of the pituitary or ovary (ie an animal implanted with an ovary/pituitary from a masculinised animal would ovulate if their hypothalamus had not been masculinized).
If the ovary or pituitary came from a non masculinized animal and was implanted into a masculinized animal (with it’s masculinized hypothalamus), there was no ovulation
Therefore the source of sexual differentiation is the hypothalamus.
