normal puberty

Normal Puberty

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Physiology of PubertyPeriod of Infancy and Childhood:

the hypothalamic-pituitary system (the “gonadostat”) is highly sensitive to negative feedback of estrogen (estrodiol concentrations are as low as 10 pg/ml)

gonadotropins and gonadal steroids remain at very low levels until age 6-8

FSH and LH remain low but are still secreted in pulsatility


Physiology of Puberty

Prepubertal Period:

3 critical changes in the low endocrine state of childhood emerge:

1. Adrenarche

2. Decreasing repression of the “gonadostat”

3. Gradual amplification of the GnRH-gonadotropin interaction


Physiology of PubertyAdrenarche (aka Pubarche)

Increase in production of adrenal androgens resulting in growth of pubic and axillary hair. Precedes menarche by 2 years

Mechanisms initiating adrenarche are NOT associated with the mechanisms initiating gonadarche Evidence *Kallman’s syndrome: adrenarche occurs despite absence of gonadarche*Addison’s Dz: gonadarche occurs despite absence of adrenarche*Precocious Puberty: gonadarche precedes adrenarche

Initiating Mechanisms:

Suggested factors:1. Pituitary adrenal androgen stimulating factor2. Local steroid inhibition of key enzymes within the adrenals

**Mechanisms still remain unclear **Adrenarche may be simply the attainment of a level of maturation that requires a particular

amount of time.



Decreasing Repression of the “Gonadostat”

Mechanisms:

1. Decreasing the negative feedback of low levels of gonadal estrogen on hypothalamus and pituitary sites

2. Decreasing the intrinsic central inhibitory influence on GnRH

Neuropeptides involved in inhibition: GABA and neuropeptide Y



Alteration of GnRH-Gonadotropin Interactions:

increased amplitude and frequency of pulsatile GnRH provoke progressively enhanced responses of FSH and LH.

FSH levels rise, then plateau in midpuberty and LH levels rise slowly, then peak in late puberty

Increases in gonadotropin secretion stimulates increased secretion of estrogen.

Dichotomous Effects of Estrogen Feedback

Positive Feedback: increases LH secretory response to GnRH

Negative Feedback: combines with inhibin to inhibit FSH response


Timing of Puberty

Major Determinant: Genetics good correlation of times of menarche of mothers and daughters and between

sisters

Minor Determinant: Nutritional status general health geographic location **Children in urban areas, closer to the equator, at lower altitudes, mildly obese start

puberty earlier

Role of Total Body Fat in Timing of Puberty-controversial

Argument: critical body weight must be reached to achieve menarche.

Supportive Evidence: moderately obese girls have earlier menarcheOpposing Evidence: morbidly obese girls and intense exercisers with normal

weight have delayed menarchewww.freelivedoctor.com

Timing of Puberty

Leptin proposed hormone responsible for initiation and progression of puberty produced by adipocytes serum leptin concentration correlated to body fat content

Observations1. Mice deficient in leptin fail to undergo puberty2. Fertility is restored if leptin-deficient mice are administered the hormone3. Leptin inhibits neuropeptide Y gene expression

Leptin levels increase in puberty, suggesting a threshold level of leptin (and therefore a critical amount of adipose tissue, the source of leptin)

*the higher levels of leptin, the earlier the age of menarche*girls with idiopathic precocious puberty have higher levels of leptin


Stages of Pubertal Development

Pubertal Sequence

Accelerated growth→breast development→adrenarche→menarche

requires 4.5 years (range 1.5 to 6 years)


Signs of Puberty: Tanner Staging

Stage 1 (Prepubertal)

Elevation of papilla only. No pubic hair.

Stage 2 Elevation of breast and papilla as small mound, areola diameter enlarged. Median age: 9.8

Sparse, long, pigmented hair, along labia majora. Median age: 10.5

Stage 3 Further enlargement without separation of breast and areola. Median age: 11.2

Dark, course, curled hair sparsely spread over mons. Median age: 11.4

Stage 4 Secondary mound of areola and papilla above the breast. Median age: 12.1

Adult type hair, abundant but limited to mons. Median age: 12

Stage 5 Recession of areola to contour of breast. Median age: 14.6

Adult type spread in quantity and distribution. Median age: 13.7


Tanner Staging


Growth average girl reached growth peak 2 years after breast budding and one year

prior to menarche

*limited growth potential after menarche

due to estrogen and concomitant increase in growth hormone

peak bone mineralization occurs as well.

*half total body calcium laid down during puberty.

calcium supplementation during adolescence results in increase bone density

(GIVES PROTECTION AGAINT FUTURE OSTEOPOROSIS!!)


Menarche age of menarche chiefly controlled by

genetics

environmental factors important: improving nutrition produces taller, heavier girls

Trend toward lowering the menarchal age and puberty halted in the 1960s.

Median age of menarche in U.S. is 12.8

Menses are usually anovulatory for 12-18 months after menarche


normal puberty

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