Hormones, growth and sexual development

Question 1

chemical classification of hormones

Answer 1

1. Amino acid based: synthesised from tyrosine
   
   • Most hormones are amino acid based.
   • Simple amino acid derivatives like adrenaline
2. Steroids: synthesized from cholesterol.
   Of the hormones produced by the major endocrine organs, only gonadal and adrenocortical hormones are steroids.
3. Peptide/protein: synthesised as prohormones
   
   • Vasopressin/ADH/AVP

Question 2

function hormones

Answer 2

• All major hormones circulate to virtually all tissues, but a hormone influences the activity of only those tissue cells that have receptors for it –> target cells
  • Alters plasma membrane permeability or membrane potential, or both, by opening or closing ion channels
  • Stimulates synthesis of enzymes and other proteins within the cell
  • Activates or deactivates enzymes
  • Induces secretory activity
  • Stimulates mitosis

Question 3

hormonal signalling

Answer 3

• Water-soluble hormones (all amino acid–based hormones except thyroid hormone) act on receptors in the plasma membrane.
  • These receptors are usually coupled via
  regulatory molecules called G proteins to one or
  more intracellular second messengers which
  mediate the target cell’s response.
• Lipid-soluble hormones (steroid and thyroid hormones) act on receptors inside the cell, which directly activate genes.

Question 4

childhood growth

Answer 4

mostly regulated by GH, IGF-1, ghrelin and thyroid hormones

Question 5

thyroid hormones and growth

Answer 5

• Release of thyroid hormone plays a large role in childhood growth:
  
  1. Hypothalamus gets a stimulus: cold weather, pregnancy, high altitude and hypoglycaemia, and something during childhood (not known)
  2. Hypothalamus releases thyrotropin-releasing hormone (TRH)
  3. The anterior pituitary now releases thyroid-stimulating hormone into the bloodstream
  4. TSH stimulates the thyroid gland to release thyroid hormone (T3 and T4)
  5. TR then acts on target cells:
     • All cells (especially neurons  increased metabolic rate
     • Liver  more glucose formation
     • Adipose tissue  increased lipolysis
     • Lungs  increased ventilation
     • Heart  increased heartrate and contraction force
     • Bone  stimulate chondrocyte maturation, overall osteoblast activity
     • Skeletal muscle  stimulates protein synthesis and degradation

Question 6

growth hormone (and IGFs) and growth

Answer 6

1. Hypothalamus releases growth hormone releasing hormone
2. GHRH causes anterior pituitary to release growth hormone
3. GH stimulates hepatocytes to release insulin like growth factors
4. IGFs and GH then act on target cells:
   • Liver –> more glucose
   • Adipose tissue –> lipolysis
   • Bone:
   GH: Stimulates epiphysial growth
   GH: Increased osteoblast differentiation and activity
   GH: Increased endochondral bone formation
   GH: Stimulates local IGF-1 production
   IGF: Increased epiphyseal chondrocyte proliferation
   and hypertrophy (growth)
   IGF: Osteoblast differentiation
   IGF: Increased bone density
   • Skeletal muscle:
   GH: Increased AA uptake and thus protein synthesis
   GH: Increased lean tissue mass
   IGF: Increased hypertrophy
   IGF: Inhibit protein catabolism

Question 7

male growth spurt

Answer 7

1. Hypothalamus produces GnRH
2. GnRH causes the anterior pituitary to release LH and FSH
3. LH –> Leydig cells –> androgens –> Sertoli cells –> oestrogens
4. FSH –> Sertoli cells –> ABP
   - Adipose tissue produces oestrogen
   - In males testosteron and oestradiol cause the growth spurt
   - Men grow larger due to later closing of the epiphyseal plate (is closed by oestrogen)

Question 8

Female growth spurt

Answer 8

1. Hypothalamus produces GnRH
2. GnRH causes the anterior pituitary to release LH and FSH
3. LH –> theca cells –> androgens
4. FSH –> granulose cells –> oestrogens
   - Prolonged exposure of oestrogens/progesterone to the hypothalamus causes a decrease of GnRH while a short exposure causes increased secretion of GnRH
   - Theca cells and granulosa cells both produce progesterone, the progesterone form granulosa cells diffuses into the theca cells to be converted into androgens, the androgens then diffuse back to the granulosa cells to be converted by aromatase to oestrogens –> oestrogens cause the growth spurt in females

Question 9

puberty onset

Answer 9

• Kisspeptin and leptin (from adipose tissue) are needed to start puberty
• It is thought that high expression of MKRN3 (an E3 ligase) in the hypothalamus is what keeps kisspeptin-expressing neurons inhibited before puberty
  • The expression of MKRN3 drops towards puberty alleviating the inhibition of these neurons by allowing high expression of kisspeptin and neurokinin B (MKRN3 ubiquitinated these before puberty)
  • Kisspeptin and neurokinin B cause increased release of gonadotropin-releasing hormone from the hypothalamus
  • GnRH causes release of luteinizing hormone and follicle-stimulating hormone from the pituitary gland
  • LH and FSH cause production of oestrogen by the ovaries and testosterone by the testes

Question 10

stimulation of GnRH neurons

Answer 10

• Kisspeptin and KNDy neurons stimulate GnRH neurons
• GnRH neurons lack steroid hormone receptors Kiss and KNDy neurons have them
  1. steroids bind to them and cause release of Kisspeptin and KNDy neurotransmitters
  2. they stimulute GnRH release from hypothalamus
  3. LH and FSH release from pituitary
  4. steroid release from follicles/testes
  5. these steroid can now bind agin to the Kiss and KNDy neurons –> lenth of exposure decides +/- effect on these neurons
  6. additionally, leptin stimulutes GnRH neurons and ghrelin inhibits them

Question 11

mentrual cycle

Answer 11

1. GnRH from hypothalamus –> LH and FSH from pituitary
2. FSH –> granulosa cells –> oestrogens
3. LH –> thecal cells –> andorgens –> granulosa cells –> oestrogens
4. this rise in LH and FSH causes the follicles to produce oestrogen this inhibits the hypothalamus and pituitary to stop LH and FSH release causing only 1 follicle to mature
5. once this follicle is matured it produces large amounts of oestrogens which now have a positiv feedback on LH and FSH producion –> gonadotropin burst
6. the LH surge causes ovultion to occur
7. after ovultion oestrogen levels decline and teh ruptured follicle becomes the corpus luteum
8. LH stimulates the corpus luteum to release progesterone inhibin and a lil oestrogen
9. these are a strong negative feedback on the hypothalums and pituitary to inhibit teh maturation of a new follicle during pregancy
10. when there is no fertilisation the egg is lost and LH drops causing corpus luteum degradation and a drop in oestrogen and progesterone
11. GnRH release adn new cycle starts

Question 12

spermatogenesis

Answer 12

1. GnRH from hypothalamus –> LH and FSH from pituitary
2. FSH –> sertoli cells –> andorgen binding protein (test concentration maintenance)
3. LH -> leydig cells –> testosterone and a lil oestrogen
4. testosterone –> spermatogensis and more effects throughout body (muslce and bone growth, etc.)
5. test inhibits the hypothalamus and pituitary
6. sertoli cells produce inhibin when sperm count is high –> negative feedbcak to hypothalamus and pituitary