PHY3181 Lecture Notes - Lecture 3: Spermiogenesis, Meiosis, Squamous Metaplasia
30 Jun 2018
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Lecture 4: Male reproductive endocrinology
The endocrine system is a collection of glands
that synthesise and secrete hormones into the
bloodstream where they act on organs/
tissues. Note that there is no ductal system.
Classes of hormones
• Peptides eg GnRH
• Protein/ glycoprotein eg LH and FSH
• Steroids (derived from cholesterol) eg
testosterone and estrogen
• Amino acid derivatives eg NA (amino
acids with modifies groups)
The aging male: testosterone and the HPG
axis
Levels of testosterone decline after 50. LH
basal levels increase in older men; LH pulsitility
is blunted. Steroidogenic capacity of the leydig
cells decreases. spermatogenesis: lower
fecundity at >40 years, 50% lower probability
of achieving pregnancy within 1 year compared
to males <25 years.
Note that testosterone levels change a lot
throughout development there is a massive
spike at puberty that stays very active during
adulthood these levels will then decline
(may use T therapeutically)
*************************************L
ocal steroid signalling via nuclear receptors
• Steroids are lipophilic can pass
through the membrane
In nuclear receptors:
• All have the same consensus sequence
(domains) eg ligand binding domain –
is relatively consistent
• The greatest variability in the nuclear
receptors is in the N-terminal domain.
The N-terminal domain is what affects
how it does downstream signalling
Classical nuclear receptor signalling
1. Steroids in the blood are not free
floating, they ae bound to a protein
carrier (this is because they are not
water soluble)
2. Once released from the protein carrier
the steroid hormone can move
through the cell membrane
3. Once in the cytoplasm finds the
nuclear receptor complex the
nuclear receptor is bound to a protein
eg HSP
4. HSP gets released
5. Nuclear receptor hormone complex is
formed form a dimer
6. The dimer can move through the
nuclear pore moves into the
nucleus and finds the DNA
7. When it reaches the DNA it alters gene
transcription
8. mRNA protein that changes cell
function is made
note that in the nucleus there are coactivators
and corepressors
• coactivators bind to the androgen
response element on the DNA – can
switch on or off gene expression
note that the hormone may also go straight
into the nucleus before meeting their receptor
protein.
Drugs can be designed to target different parts
of this pathway (hence why it is important to
understand all steps)
Non-classical nuclear receptor signalling
These are the non-genomic effects, they may
be ligand dependent or ligand independent
Ligand dependent
Document Summary
The endocrine system is a collection of glands that synthesise and secrete hormones into the bloodstream where they act on organs/ tissues. Classes of hormones: peptides eg gnrh, protein/ glycoprotein eg lh and fsh, steroids (derived from cholesterol) eg testosterone and estrogen, amino acid derivatives eg na (amino acids with modifies groups) The aging male: testosterone and the hpg axis. Lh basal levels increase in older men; lh pulsitility is blunted. Steroidogenic capacity of the leydig cells decreases. lower fecundity at >40 years, 50% lower probability of achieving pregnancy within 1 year compared to males <25 years. spermatogenesis: Note that testosterone levels change a lot throughout development there is a massive spike at puberty that stays very active during adulthood these levels will then decline (may use t therapeutically) *************************************l ocal steroid signalling via nuclear receptors: steroids are lipophilic can pass through the membrane.
