W2L3 Fri puberty Flashcards

1
Q

What is Puberty

A

Onset of the reproductive years
* Period when secondary sexual characteristics develop and potential for sexual reproduction
Changes are endocrinological, physiological, morphological, behavioural
Sexual and reproductive development occurs in 3 main ways: Accelerated growth, Differential growth, Sexual dimorphism
Period of increased levels of steroid hormones marked by:
Menarche- first menstruation
First ejaculation

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2
Q

Pubertal timing and growth

A

Lasts 3-4 years – humans
*start at 9-14 years old in female
* start at 11-15.5 years in male
-Changes in rate of growth and increase in bone density
In girls, starts earlier and finishes earlier (oestrogen closes epiphyses faster –> shorter bones in female)
In boys, starts 2 years later when they are already 7 cm taller
*Similar but not the same sequence of developmental changes in boys and girls
* Sex dimorphism in body shape- shoulders, hips
* Driven by Growth Hormone and sex-steroids (oestrogens and androgens)

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3
Q

Trend to earlier puberty

A

*Decrease in age of puberty in the last 180 years
* Changes in living conditions, health care and nutrition
* Changes not seen in most underdeveloped countries
* Trend slowed in last 40 years??

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4
Q

What triggers puberty

A

Growth hormone (critical) – acceleration of body
growth – increase body weight:
Attainment of about 47kg in girls and about 55kg in boys
Obesity- girls experience earlier menarche, boys delays puberty
Underweight ballet dancers and girls/boys with anorexia nervosa – primary amenorrhea in girls (slower puberty)
Still variation between individuals- genetics
Body weight/Nutrition interaction to ‘turn on’ puberty
Environmental stimuli, psychological stress, pheromones, photoperiod, temperature (more relevant to animals)
Maturation of central nervous system (CNS)-Hypothalamus

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5
Q

Level of puberty control

A

Hypothalamus : GnRH oscillator (pulse generator) and Frequency of pulses
Portal vessel: pulsating hormone signal
Pituitary: Frequency and amplitude modulated,
Gonads: Activation of gonadal gonadotrophin receptors, Amplitude modulated, Act via gonadal steroid receptor

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6
Q

Gonadostat Hypothesis

A

Before puberty, very low threshold of gonadalsteroids regulating the negative feedback action
* At puberty, hypothalamus-pituitary becomes less sensitive to gonadal steroids
* GnRH levels increase – gonadotrophins increase – gonads response increases – increased steroid levels
* Reflects changing characteristics in the HPG feedback system, but may be consequence rather than cause of puberty

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7
Q

Maturation of CNS experiment on monkey

A

Shown by studies in other species- higher primates
Induction of gonadotrophin pulses in immature pre-pubertal rhesus monkey by hourly GnRH pulses over 110 days
Note the first induced oestradiol peak does not induce a full LH surge
After cessation of GnRH pulses ovarian cycles cease and subsequent implantation of an oestradiol pellet does not induce an LH surge in the absence of GnRH pulses

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8
Q

Activation of the HPG axis

A

Maturation of hypothalamus-pituitary-gonads axis:
1. Increased production of GnRH
2. Increased sensitivity of gonads to FSH and LH
3. Increased production of gonadal steroids, E2, T, P4
4. Increased response of CNS to steroids – maturation, self perpetuating

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9
Q

Kisspeptin

A

Discovered to regulate HPG axis in 2003
Various peptides derived from a 145 a.a. protein encoded by KISS1 gene
Found in hypothalamus
Act via G-protein coupled receptor Kiss1r (GPR54)
Kiss1r found on GnRH neurons
Exogenous kisspeptin stimulates GnRH secretion
Mice with disrupted Kiss1 or Kiss1R prevents puberty
Onset of Kiss1 expression in hypothalamus and increased Kiss1r in GnRH neurons just before puberty
Administration of kisspeptin to prepubertal rats advances onset of puberty

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10
Q

Kisspeptine activation

A
  • sex steroid activate kisspetinine neuron in the aVPV lead to stimulation of the GnRH neuron, release GnRH to the pituitary gland
    -sex steroid bind to accurate nucleus would represse kisspetine neuron activaiton
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11
Q

Organ systems involved in pubertal change

A

Adrenal system
Neuroendocrine system
Reproductive system - Development and maturation of primary and secondary features
Musculoskeletal & Nervous systems
- General growth and remodelling of body shape (androgen, oestrogen)
- Sensitivity, pleasure sensation, parasympathetic and sympathetic for arousal and ejaculation
Respiratory system- Growth of the larynx and deepening of male voice (androgen)
Integumentary system- Development and growth of hair, sweat and sebaceous glands and hypodermis
Cardiovascular system- Increase blood volume (androgen), increase interstitial fluid (oestrogen)

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12
Q

Adrenal system

A

Adrenal changes (Adrenarche)
* From 8 years old until about 13-15 years
* Increased secretion of dehydroepiandrosterone DHEA and DHEAS (DHEA-sulphate)
* Weak androgens but very high concentrations
* Independent of glucocorticoid and mineralocorticoids
* Promotion of pubic and axillary hair growth
* Not closely linked to puberty
* Not really understood its role, not essential for puberty

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13
Q

Neuroendocrine system activation during puberty

A

In both male and female, re-activation of HPG axis:
-Increased GnRH pulses first start at night, heralds pubertal onset, then continue during the day time
-In response, LH level is increased, in mid-late pubertal time, LH level is higher than in adult
-This axis also produces growth hormones, prolactin, adrenocorticoids
-Coordination of all pubertal changes between nervous, endocrine and reproductive systems

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14
Q

Female Reproductive endocrinology at puberty

A

Pubertal period, 9-14 years old
Increased levels of gonadotrophins (FSH, LH) and E2 with pubertal stage and bone age
* Steroid-driven sexual response
Before puberty, ovary contains small primordial follicles and few larger ones
At puberty, enhanced follicular development, ovulation, corpus luteum formation
Significant increase in ovarian size

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15
Q

Female development during puberty: Tanner Stages

A

Pubertal changes due to oestrogens (Thelarche)
Endometrial proliferation and thickening – menstruation, first menarche without ovulation
Breast development is the first sign of girl’s puberty- initiated by oestrogen, prolactin, growth hormone
Mostly fat deposition rather than glandular tissue and budding and growth of breast ducts

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16
Q

Male Reproductive Endocrinology at Puberty

A

Pubertal period, 11.5 - 15 years old
Increased levels of gonadotrophins (FSH, LH) and T with pubertal stage and bone age
* Androgen driven sexual response
-Before puberty, testis contains small seminiferous tubules with relatively few germ cells and no lumen
-At puberty, Sertoli and germ cell proliferation, Leydig cells development
-Increased testicular size (first sign) 1st ejaculation without spermatozoa

17
Q

Male development during Puberty: Tanner stage

A

Male larynx grows by one third of its adult size, laryngeal prominence growth
Thickening & lengthening of vocal cords (androgen) –lowering voice pitch

18
Q

Androgen driven changes in Puberty: Female & Male

A

Classification by Tanner stages
Increased size of the genitalia Pubic, axillary, chest/facial hair
- Males: viralisation
- Females: adrenal androgen
Androgen driven changes in Puberty: Female & Male
Activation of sebaceous glands (acne) (androgen + oestrogen)
Development of axillary and anogenital “sweat” glands

19
Q

Musculoskeletal system

A

Before puberty, same proportion of muscles and fat between sex
Accelerated bone and muscle growth (androgen) and closure of epiphyses (oestrogen)
Sexual dimorphism in growth curves – men are ~ 13 cm taller
* Large pelvis (female, oestrogen) and shoulder (male, androgen)
* Men have x1.5 more lean body mass and x1.5 more skeleton than women but women have x2 more body fat (proportional)

20
Q

Neural and Nervous system

A

Fluctuating hormones and asynchronous maturation of brain regions
Mental maturation (independence, intelligence, leadership)
Increased incidence of depression, conflict, mood swings, suicidal intent (peer pressure, social / cultural intimidation)
Sexual drive
* Orgasm and pleasure sensation (intercourse), Guilt feeling (e.g. masturbation)
Sexual behaviour
* In male, active / aggressive (erection, ejaculation)
* In female, passive / receptive

21
Q

Precocious Puberty

A

5% of the population show abnormal timing of puberty: either precocious or delayed
Precocious puberty is the development of secondary sexual characteristics before:
* 8 years in girls (normally 9-13 years), 1 year earlier
* 9 years in boys (normally 11-15 years), 2 years earlier

22
Q

Type of precocious puberty

A
  1. Gonadotrophin-independent (also known as Peripheral Precocious Puberty)
    1/5th of central precocious puberty increased gonadal steroid secretion caused by:
    * testicular disorders and tumours
    * ovarian disorders and tumours increased adrenal androgen in male
    Gonadotrophin-dependent (also known as central precocious
    puberty):
    Early reactivation of HPG axis, central puberty
    Most common in girls
    Increased production of GnRH / gonadotrophins
    Caused by:
    * CNS tumours ,Other pathology OR lesions (Idiopathic)
    * 2/3rd of gonadotrophin-dependent
    * 90% of girls precocious puberty