Feb 27th Flashcards
What is the melanocortin system derived from?
Pro-opiomelanocortin (POMC).
What are the four posttranslational peptides of the melanocortin system?
α-MSH, β-MSH, γ-MSH, and ACTH.
How many melanocortin receptors exist?
Five (MC1R, MC2R, MC3R, MC4R, MC5R).
What kind of receptors are melanocortin receptors?
7-membrane, G-protein-coupled receptors (GPCRs).
What are the two melanocortin antagonists?
Agouti and Agouti-related protein (AGRP).
What are the two proteins that modulate melanocortin activity?
Mahogany and Syndecan-3.
What opioid peptide is produced from POMC but not part of the melanocortin system?
β-Endorphin (pituitary, blocks pain).
posttranslational processing of POMC is tissue-specific because:
- Different POMC peptides produced by different cell types
- Control of range of many physiological functions by same prohormone
- Mutations in POMC gene/processing rare but possible
What effect does α-MSH produced in the brain have?
It inhibits food intake.
What happens when there is a mutation in brain α-MSH?
It results in early-onset diabetes.
How does α-MSH affect skin?
It acts on melanocytes, which influence skin and coat color.
What happens when there is a mutation in α-MSH production in the skin?
It results in altered pigmentation.
Where is MCR (melanocortin receptor) produced?
In the adrenals, skin, brain, and penis.
What is a penile MCR mutation associated with?
Sexual function and dysfunction.
What effect does α-MSH have on skin pigmentation?
It increases dark pigment in the skin.
Which receptor does α-MSH bind to?
MC1R (Melanocortin 1 Receptor).
What signaling pathway does MC1R activation trigger?
G-protein-coupled receptors → cAMP → PKA → CREB.
What transcription factor does the MC1R triggered pathway lead to the synthesis of?
MITF (Microphthalmia-Associated Transcription Factor).
Which genes does MITF influence that affect pigmentation?
Tyr (Tyrosinase) & DCT (Dopachrome Tautomerase).
How does the Agouti protein affect skin pigmentation?
It antagonizes MC1R, leading to yellow pigmentation.
How does the Agouti protein affect the brain?
It antagonizes MC4R, leading to overeating & obesity.
what causes red hair
2 copies of a recessive mutation in the MC1R protein
What receptor mutation is linked to erectile dysfunction?
MC4R mutation.
What type of drugs can be used to treat erectile dysfunction related to MC4R?
α-MSH analogs.
what is and how does Melanotan II work?
- It is an example of an α-MSH analog used for erectile dysfunction
- It binds to MC3R & MC4R in the brain to increase sexual function.
What are mammary glands composed of?
7-10 lobes divided by adipose tissue.
What structure within mammary glands secretes milk?
Alveoli within lobules.
Trace the milk flow from alveoli to the nipple.
Alveoli → Secondary tubules → Mammary ducts → Lactiferous duct → Nipple.
What hormones stimulate mammary gland growth during pregnancy?
Estrogen & progesterone from the placenta.
What hormonal changes occur after birth to initiate lactation?
Estrogen decreases, prolactin increases.
Which hormone controls milk production? what triggers it?
Prolactin from the anterior pituitary.
- triggered by suckling stimulus
Which hormone controls milk release? what triggers it?
Oxytocin from the posterior pituitary.
- triggered by suckling stimulus, visual/auditory cues, or even the thought of the child
what nutrients does breastmilk contain
- proteins
- lipids
- carbs
- Vitamin A, B, D, E
- calcium, iron, zinc, selenium, etc
- immunoglobin A
- hormones, growth factors, chemokines
What does SRY stand for?
Sex-determining region of the Y chromosome.
Where is the SRY gene located?
On the Y chromosome of all animals (highly conserved).
What is the function of the SRY gene?
Induces embryonic gonads to become testes.
What happens in the absence of the SRY gene?
Embryonic gonads develop into ovaries (biological female).
What is the fetal reproductive system like at 6 weeks?
Bipotential primordium (undifferentiated reproductive structures).
What determines male development at 10 weeks?
Presence of the SRY protein, which leads to testes formation.
What does MIF (Müllerian Inhibition Factor) do in males?
It causes the Müllerian duct to degenerate and maintains the Wolffian duct.
What male structures develop from the Wolffian duct?
Seminal vesicle, vas deferens, and epididymis.
What determines female development at 10 weeks?
Absence of the SRY protein, leading to ovary formation.
Why does the Müllerian duct persist in females?
There is no MIF, so the Wolffian duct degenerates, and the Müllerian duct remains.
What female structures develop from the Müllerian duct?
Fallopian tubes, uterus, and vagina.
How do male and female external genitalia compare in early development?
They are identical during the first 6 weeks, consisting of a common urogenital sinus, genital tubercle, urethral folds, and labioscrotal swellings.
What role do testes play in external genitalia development?
Testosterone secretion masculinizes structures, leading to the formation of the penis, penile urethra, prostate, and scrotum.
What happens in the absence of testosterone?
The genital tubercle forms the clitoris, and the labioscrotal swellings become the labia majora instead of the scrotum.
How many chromosomes do nucleated body cells have?
46 chromosomes (diploid), consisting of 22 homologous pairs of autosomes and 1 pair of sex chromosomes.
How many chromosomes do oocytes and sperm contain?
23 chromosomes (haploid), which combine during fertilization to form a zygote with 46 chromosomes.
How is genetic sex determined?
Females are XX (one X from each parent), and males are XY (X from mother, Y from father).
what can abnormal SRY recombination result in
- XX male (with SRY on X)
- XY female (no SRY)
What three receptors are required for testes determination?
Insulin receptor (INSR), insulin-like growth factor 1 receptor (IGF1R), and insulin receptor-related receptor (INSSR).
What happens if all three insulin-related receptors are mutated in XY mice?
Despite having the SRY gene, they develop ovaries and exhibit a fully female phenotype.
What is a true hermaphrodite?
An individual with both ovarian and testicular tissue, with varying karyotypes and degrees of mosaicism.
What is a pseudohermaphrodite?
An individual with external genitalia of one sex but internal reproductive organs of the opposite sex.
What genetic mutation can lead to pseudohermaphroditism in males?
A defective 5α-reductase gene, which prevents the conversion of testosterone to DHT.
What is the role of 5α-reductase in male development?
It converts testosterone into DHT, a more potent androgen required for full development of male external genitalia and the prostate gland.
What is puberty?
The activation of the HPG (hypothalamic-pituitary-gonadal) axis, leading to gonadal maturation.
What happens to FSH & LH levels after birth?
They remain high for the first 6 months of postnatal life, then decline to very low levels until puberty.
What triggers puberty?
An increase in LH secretion, which becomes pulsatile.
How does LH secretion change at puberty?
The frequency and amplitude of pulses increase, with higher secretion at night than during the daytime.
What stimulates the pulsatile release of LH?
Increased secretion of GnRH (gonadotropin-releasing hormone).
What is the effect of increased LH during puberty?
It stimulates increased production of sex hormones—testosterone from the testes and estradiol from the ovaries.
How is GnRH released?
GnRH is released in pulses rather than continuously.
What happens to children with a GnRH deficiency?
They fail to sexually mature.
How must GnRH treatment be administered to be effective?
In pulses, similar to natural secretion patterns.
What is precocious puberty?
Very early onset of puberty.
