Transcript Cell signaling, endocrine and reproduction

Cell communication II:
endocrine and reproduction
3-14-2016
Hormone (hormoa; to excite) was first
assigned by Ernest Henry Starling in
1905
“The chemical messengers which, speeding
from cell to cell along the blood stream, may
coordinate the activities and growth of different
parts of the body”
Fifth stages of endocrinology
• Recognition of the gland or organ as one producing
internal secretion for physiological regulation.
• Methods of detecting internal secretion (bioassay).
• Preparation of extracts leading to a purified
hormone.
• The isolation, identification and synthesis of pure
hormone.
• Pathway biology: receptor, signal transduction and
cellular responses.
Chemical signal: proteins or small
molecules
Blood stream
Long distance
Slow response: seconds to minutes
16_12_cortisol.jpg
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Gene regulation by the thyroid hormone receptor
Three key questions will be
discussed in this lecture
• Why many hormone’s secretions are
pulsatile?
• What is the mechanism of estrogen induced
LH surge?
• Why menstru
How it happen?
Why it happen?
Optogenetics – the basic concept
• Express a light-activated ion channel (isolated
from bacteria) in a specific sub-population of
neurons
• Illuminate neurons to modulate activity
Requirement of pulsatile GnRH secretion to
stimulate pulsatile LH secretion
PNAS | December 23, 2014 | vol. 111 | no. 51 | 18387–18392
Representative 24-h GH concentration and secretion profiles
from a man (left) and a woman (right).
The Journal of Clinical Investigation 102, 153–164; 1998
J. Sleep Res. (2004) 13, 251–255
Why pulsatile insulin secretion?
Diabetes 61, 2269–2279, 2012.
In human: this is a continuous process to keep hormone level constant.
What happen to the LH when estrogen positive feedback control LH
secretion?
What causes the switch from negative to positive feedback control?
Is GnRH neuron the target of
estrogen regulation?
No!
The GnRH neuron has no estrogen receptor.
How to identify the target cells and the messages to mediate
estrogen’s dual regulation?
Schematic representation of the key pathway underlying estrogen positive
feedback in the rodent. BRAIN RESEARCH REVIEWS 57 (2008) 277 – 287.
Over 800 G protein coupled receptor
(GPCR) were found in human genome
Cloning the gene.
Looking for the possible function.
What is the ligand of GPCR?
GPR54 was cloned as orphan
receptor
Looking for the ligand. How?
Tissue distribution.
Set bioassay to purify ligand.
Kisspeptin!
What is kisspeptin?
Structural features of human kisspeptins, generated by cleavage form a common precursor,
the prepro-kisspeptin.
Suppress metastasis of
human melanoma
Manuel Tena-Sempere Hum. Reprod. Update 2006;12:631639
© The Author 2006. Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology. All rights reserved. For Permissions, please email:
[email protected]
The GPR54 gene as a regulator of puberty.
N Engl J Med. 2003 Oct 23;349(17):1614-27.
GPR54/kisspeptin and GnRH/LH
GPR54/kisspeptin
neuron
First hypothesis and current view for the central control of the HPG axis by the Kiss1 system.
Leonor Pinilla et al. Physiol Rev 2012;92:1235-1316
©2012 by American Physiological Society
Three key questions will be
discussed in this lecture
• Why many hormone’s secretions are
pulsatile?
• What is the mechanism of estrogen induced
LH surge?
• Why menstruation？
Why menstruation?
• Clean sperm carried pathogen.
• Energetics more favorable.
• To avoid maternal/fetus conflict
Menstruation: spontaneous
decidualization
• Hypothesis 1: SD evolved for early
protection against invasive fetal tissues
• Hypothesis 2: SD evolved for embryo
selection
Prevent mesnstruation and ovulation
High level
of E and P
Keep 黃體 active
CGH
urine
RU486: competitive inhibitor of the progesterone
receptor (progesterone antagonist or antiprogestins)
Birth control pill: combination of estrongen
and progesterone.
Mode of Action: prevent the pituitary from
secreting LH and stop ovulation.
Usage: take the pills for 21 days and stops
for 7 days. The fall in steroid levels
triggers menstrual flow.