Endocrinology of Puberty I Flashcards

1
Q

What is an endocrine cell?
> What triggers the function of an endocrine cell?

A
  • A cell that secretes hormones > Stimuli e.g. chemical
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2
Q

Amine hormones: (T3, T4, adrenaline, noradrenaline, dopamine, serotonin, 5-HT 5-hydroxytryptoamine)

1- How are they made? Where are they stored?

2- What do they act as?

3- What do they bind to?

A

1- Enzyme modifications on amino acids: Tryptophan + Tyrosine > Vesicles

2- Neurotransmitters in synapses within NS or endocrine mediators (hormones) in body

3-
- Cell surface receptors mainly GPCR
- T3/4 bind to Intracellular receptors
- 5-HTbinds to Ionotropic receptors

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3
Q

Protein: Follicle-stimulating hormone (FSH), Mullerian inhibiting hormone (MIH) + Peptide hormones: (GnRH, insulin)

1- How are they made?

2- Where are they stored?

3- What do they bind to?

4- Hydrophobic/ Hydrophillic?

A

1- Gene expression

2- Stored in intracellular secretory granules and released via exocytosis upon stimulation by a secretagogue

3- Specific cell surface receptors (GPCR or tyrosine kinase)

4- Hydrophilic, so mostly unbound in serum (except IGG1/2)

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4
Q

Glycoprotein hormone family:

1- Which proteins are members of the glycoprotein hormone family? What is the same and different between thes?

2- What do they bind to? Which of them bind to the same receptor? Why is this relevant?

3- Where are they produced

A

1- FSH/hCG/LH
> Same alpha chain code by same single gene on ch6
> Different beta chain

2- LH/ hCG > hCG is produced during early pregnancy to maintain activity of the LH

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5
Q

Steroid hormones: (Mineralocorticoids, glucocorticoids, sex steroids)

1- Where are they produced? What are they derived from?

2- Give 2 examples demonstrating peripheral conversion of steroids?

3- What do they bind to, what is significant about this?

4- How are they stored?

5- hydrophilic/hydrophobic?

A

1- Adrenal glands (expect oestrogen), gonads, and placenta. > Cholesterol

2- (e.g.weak adrenal androgens to testosterone by liver, adipocytes, skin or aromatization of testosterone to oestrogen in the brain)

3- Structurally related… activate the same receptors but have a different potency.

4- Not stored, synthesised when needed, by increasing activity of enzymes

5- Hydrophobic > diffuse freely across membrane whilst bound to plasma proteins e.g. albumin, androgen binding protein

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6
Q

How can endocrine activity be controlled via :

1- Hormone level/activity (4)
2- Receptor factors (4)

A

1-
- Amount of hormone produced/ secreted
- Affinity of hormone for receptor and half life in plasma (potency)
- Rate of hormone clearance
- Available transport proteins in plasma

2-
- alter activity of receptor
- alter signalling of receptor e.g. antagonists
- amount of receptors available for binding
- desensitisation of receptors upon high levels of agonist

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7
Q

1- How does hierarchal level of control regulate endocrine activity in reproductive physiology?

2- What happens under specific circumstances?

> Hypothalumus- pituitary gonad axis used as an example..

A

1- Initiated by signals from the cerebral cortex
> Negative feedback regulates this herarchic endocrine system
> Long loop (feedback from androgens to hypothalamus) and short loop (from androgens and oestrogens to anterior pituitary) feedback

2- Positive feedback can drive the axis for short period of time e.g. pre -ovulatory LH surge

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8
Q

1- What are primary sexual characteristics?
2- Name female and male primary characteristics:
- Gonads
- Internal genitalia
- External genitalia

A

1- Sexual characteristics developed during embryological and foetal developments.

2-

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9
Q

What determines the primary sexual characteristics in MALES?

A

> Sex determining region on the Y chromosome (SRY) gene initiates the differentiation of cells in the gonadal primordia ridge to become pre-Sertoli cells, which starts the development program to form testis

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10
Q

How do ovaries develop?
Is ovarian endocrine activity essential for the development of female primary sexual features?

A

> Absence of SRY
NO

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11
Q

How do we develop Ovaries and Testes?

A
  1. Migration of Primordial germ cells 4-6 weeks to Bipotential Gonadal primordia ridge allowing the tissue cells to express the SRY gene if they do have it > Testes
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12
Q

How is male internal genitalia developed?

A
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13
Q

What happens if there is a failing in testosterone and MIH hormone production?

A
  • Paramesonephric duct is going to be maintained and further developed into female internal genitalia.
  • Mesonephric duct will Degenrate as there Is no testosterone.
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14
Q

How is male and female external genitalia developed?

A
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15
Q

Progenitor cells must contain the right number of X chromosomes. What does oocyte growth and spermatogenesis require?

A
  • Oocyte growth > 2 X chromosomes
  • Spermatogenesis > 1 X chromosome
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16
Q

Testes develop in upper lumbar. How do they defend to scrotum?
Mention what happens at 15 AND 35 weeks

A
  • Lengthening & regression of suspensory ligament (cranial) accompanied by shortening of gubernaculum (Caudal)
  • Regulated via MIH + Testosterone + Insl3
  • 15: testes in close proximity to inguinal canal
  • 35 weeks: testes have reached scrotum
17
Q

What is cryptorchidism? What does it increase the risk of?

A
  • Failure in testicular descent.
    > Sub-fertility and increased risk of testicular cancer
18
Q

What does puberty describe?
- What does it activate
- What does it start the pulsation of
- what does it initiate

A
  • Transition from juvenile to a (potentially) fertile adult
  • Activation of the hypothalamus – anterior pituitary – gonad axis

> Start of pulsatile secretion of GnRH by the hypothalamus and LH and FSH by the anterior pituitary (maintain responsiveness of system)

-Initiation of sex steroid production, gametogenesis and development of secondary sexual features via endocrinological changes

19
Q
  • Why are Gonadotropin and androgens levels are very low in childhood?
  • How does the axis then become activated during puberty?
A
  • Neurons secretingg-amino butyricacid (GABA) inhibit GnRH-neurons in the hypothalamus > no GnRH release
  • Activation of pulsatile GnRH secretion is key for onset of puberty
    » more excitation than inhibition on GnRH neurons to secrete GnRH - Kisspeptin signalling
20
Q

Age at menarche in the US and Europe has decreased > Puberty starting earlier
…. Better healthcare, health, living conditions, socio economic standards
- Describe the hypothesis

A
  • Better nutrition > children reach a critical weight (stable over time) required for activation of the Hypothalamic pituitary gonadal axis sooner
  • Hypothesis: ↑ white adipocytes > ↑ leptin level > Leptin activates Kiss1 neurons > ↑kisspeptin signalling > activation of GnRH-secreting neurons > ↑ GnRH secretion
21
Q

What are some secondary sexual characteristics of males?

A
  • ↑size of testes,penis and scrotum
  • Maturation of accessory sex glands > production of seminal fluid starts
  • Facial, axillary & pubic hair growth
  • Sexual dismorphic features
22
Q

1- Compare when the growth spurt happens in males/ females

2- Final skeletal proportions results from balance between…

A

1- 2 years earlier in females

2-
> ↑ rate of longitudinal bone growth by sex steroids & GH/IGF-1 axis
> ↑ rate of epiphyseal growth plates closure by HIGH estrogens (derived from testosterone in testis and adipose)

23
Q

Puberty is not just physical changes there are also psychological and behavioural changes.
What are the effects of testosterone on behaviour?

A
  • Non primates > Castration = loss of male sexual behaviour
  • Primates , more complex

>

  • In humans Testosterone important for development of sexual behaviour ALONSIDE other factors e.g. social interactions, learning + biological
    – Non-linear… more testosterone does not mean more sexual behaviour.
24
Q

5-alpha reductase makes dihydrotestosterone from testosterone.
What are the effects of testosterone vs by dihydrotestosterone?

A
  • Activation of Sertoli cells + initiation of spermatogenesis underpins some of the testicular growth and increase in scrotum volume
25
Q

1- What initiates the process of spermatogenesis?
(Spermatozoan from Pro- spermatogonium)

2- What is the blood-testis barrier?

A

1- Start of puberty initiates spermatogenesis and it takes a few years for the male to become fully fertile. - Occurs within the seminiferous tubules

2- Develops during puberty
- Tight junctions around Sertoli cells
- Maintains intratubular fluid composition & protects spermatids from the immune system

26
Q

1- What are Sertoli cells?
2- What is their function?

A

1-
- Supporting cells of the seminiferous tubules
- “nurse” the gametes

2- Initiated via FSH and testosterone
> Support and regulate spermatogenesis
> Secrete androgen binding protein to increase concentration of testosterone in the seminiferous tubules
> Phagocytose any excess/waste plasma from spermatogenesis
> Secrete inhibin which can inhibit pituitary release of FSH via negative feedback
> Cyclic variation in receptors for androgens in Sertoli cells = regulation of spermatogenesis

27
Q

Describe the production of spermatozoan.

A

> Spermatocytogenesis :
Pro-spermatogonium → spermatids

> Spermiogenesis
Spermatids → spermatozoa

*NOTE: During mitosis & meiosis, cytokinesis is incomplete – primary spermatocytes derived from a single spermatogonium are linked via cytoplasmic bridges

28
Q

What is spermiogenesis? (5)

A
  • Cytoplasmic and further maturation of genetic remodelling leading to distinctive morphology.
    > Compact DNA in head
    > Absence of cytosol
    > Head topped by acrosome
    > Mid piece : mitochondria
    > Tail
29
Q

1- What is the temporal organisation of spermatogenesis?

2- What is the spermatogenic cycle?

A

1- Spermatogenesis takes a constant 64 days in humans
- 16-18 days, from Type A to Type B spermatogonium
- 23 days to form primary spermatocytes
- 1 day for secondary spermatocytes
- 23 days for spermiogenesis

2- Mitosis of type A spermatogonium starts every 16 days

30
Q

1- What is the spatial organisation of spermatogenesis?

A

1- Sperm production (and thus fertility) is constant
> A single tubule produces spermatozoan all the time, but these develop from different segments within the tubule (spermatogenic wave)
> Sequential arrangement of different stages of germ cell development, forming a wave-like pattern

31
Q

What makes an ideal male contraceptive?

A
  1. As effective as female contraceptive
  2. Acceptable by both partners
  3. No interference with libido or sexual activity
  4. Works fast, fully reversible
  5. No toxic side effects
  6. Not harmful to offspring
32
Q

What research is there for male contraceptions at the moment? (5)

A
  • Vitamin A inhibitors to prevent spermatogenesis
  • Polymer occlusion of vas deferens
  • Inhibition of sperm motility
  • Endocrine inhibition of hypothalamus-pituitary-testis axis
  • (Mild heat)
33
Q

What are hormonal approaches to male contraception?

A

We want to get < 1 million spermatozoa / mL of semen
* Inhibition of hypothalamus–anterior pituitary–testis axis
* ↓ testicular production of testosterone >↓ [testosterone] in testis > ↓ spermatogenesis

BUTTT we need to maintain Sufficient systemic [testosterone] > libido, potency, sexual characteristics, bone health