DR. NOR ASHIKIN 03/09 year 1 Endocrine control of puberty in males • The testes secrete substantial amounts of testosterone in the 1st trimester of fetal development and in the 1st few month of infancy. • The testes then becomes dormant for the rest of infancy and childhood • From puberty to adulthood, reproductive functions is regulated by hormonal links between the hypothalamus, pituitary gland and gonads (the brain-testicular axis) Endocrine controls of puberty in females • Puberty is triggered by the same hypothalamic pituitary hormones in girls as it is in boys • Rising levels of GnRH stimulate the ant lobe of pituitary to secrete FSH & LH • FSH help develop the ovarian follicles, which in turn secrete estrogen, progesterone, inhibin and a small amount of androgen • These hormone levels rise gradually from ages 8 – 12 and more sharply early teens Estrogens (estradiol, estriol & estrone) are feminizing hormones with widespread effects on the body. Estradiol results in the most visible changes.

Endocrine control of puberty • The 1st demosratable biological change of puberty is the appearance of pulsatile LH release during sleep • As puberty progresses, the frequency and amplitude of LH peaks increase • At the end of puberty, the difference b/t sleep & wake LH pattern disappear • • • • • The LH surge is triggered by the increasing activity of neurons that release GnRH GnRH cause the ant pituitary to release gonadotrophins, LH & FSH The factor that cause the hypothalamus to start secreting GnRH/ the activation of the axis is uncertain The precise trigger for the GnRH surge during puberty is not known The influence of adequate nutrition has long been known Hypothesis – when adequate body fat distribution has been attained (17% body fat for female), a signal is sent to hypothalamus to trigger release of GnRH

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Leptin is probable hormone that trigger GnRH surges during early puberty GPR54 gene appears to be critical for the normal development of puberty. It encodes a protein that appears to have an effect on the secretion of GnRH by the hypothalamus Multiple factors are probably involved

Timing of onset of puberty • The onset of puberty varies among individuals • Puberty usually occurs - In girls the ages of 10 and 14, while - In boys it generally occurs later, b/t the ages of 12 and 16 Adolescent girl’s reach puberty at earlier ages than were ever recorder previously. Nutritional and other environmental influences may be responsible for this changes

Five phases in puberty 1. Adrenarche • Adrenarche refers to a stage of maturation of the cortex of the human adrenal glands. Increase in the secretion of adrenal androgens • It typically occurs b/t ages 6 and 10 and involves both structural and functional changes Adrenarche is a process related to puberty but distinct from hypothalamic-pituitarygonadal maturation and function 2. Gonadarche • It refers to the earliest gonadal changes of puberty. In response to pituitary gonadotropins, the ovaries in girls and testes in boys begin to grow and increase the production of the sex steroids, especially estradiol and testosterone • In boys, testicular enlargement is the 1st physical sign of gonadarche, and usually of puberty • In girls, ovarian growth cannot be directly seen, so thelarche and growth are usually the first evidence of gonadrche 3. Thelarche • It is the first stage of secondary (postnatal) breast development, usually occurring at the beginning of puberty in girls • Thelarche is usually noticed as a firm, tender lump directly under the centre of the nipple (papilla and areola) • It is also referred to as a “breast bud”, or more formally as Tanner stage 2 development • It may occur on one side first, or both sides simultaneously 4. Pubarche • It refers to the 1st appearance of pubic hair in children Pubarche is one of the physical changes of puberty but should not be equated with it since it may occur independently of complete puberty • It usually result from rising level of androgens from the adrenal glands or testes but may also result from exposure of a child to an anabolic steroids 5. Menarche • It is the first menstrual period, or first menstrual bleeding in females •

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It is considered the central even of female puberty, as it signals the possibility of fertility Timing of menarche is influenced by both genetic and environment factors, especially nutritional status The average age of menarche has declined over the last century

Effects of gonadotropins 1. FSH • Males – stimulates spermatogenesis and spermiogenesis by stimulating Sertoli cells

Females – stimulates follicles maturation, is required for follicular progression to 2nd stage and begin to secrete estradiol

2. LH • Males – increase testosterone secretion by stimulating Leydig cells. LH is required for spermatogenesis because it required testosterone • Females – a surge of LH causes the mature Graafian follicle to ovulated & transform into a corpus luteum 3. Testosterone Prenatal • Inhibits development of Mullerian structures (female internal accessory organs) • • Masculinizes external genitalia Establish male pattern of steady release gonadotrophins after puberty

4. Estrogen At puberty • Establish females pattern of body fat deposition, bone growth (increased width of pelvis and hips) and body hairs • Stimulates growth of external genitalia, internal accessory sexual organs and maintain them in functional state • Stimulates growth of breast, particularly the ductal system • Stimulates growth of uterine endometrium during follicular phase of female cycle 5. Prolactin • Plasma prolactin concentrations are low throughout childhood in boys, but significantly higher nocturnal prolactin peaks are found in early puberty (P2 – P3) • In girls, prolactin levels increase by 14 to 15 years of age, most likely due to concomitant increase in plasma estrogen 6. Growth hormone • GRF increase during puberty, particularly at night • Puberty is delayed in patients with GH deficiency • • GH plays a role in pubertal development IGF-1 is an important modulator of growth during childhood and adolescent. It increase at the time of pubertal growth acceleration

7. Insulin • Insulin is also important in normal growth • • • Plasma insulin levels increase throughout childhood but rise is more during puberty Insulin sensitivity decreases in puberty, therefore requirement for insulin increase Peak velocity of puberty results from the combined action of sex steroids, GH, IGF-1 and probably insulin

Medical concern during puberty 1. Precocious puberty • Puberty can occurs earlier than usual • Medical evaluation for it should be performed if breast/ pubic hairs development occurs prior to age 7 in Caucasian girls or prior to age 6 in African American girls • Boys who show signs of developing secondary sex characteristics prior to age 9 are also considered to have it. It can be associated with psychological difficulties that may impact a child’s emotional development • It is much more common in girls than in boys. Many girls experience it in the absence of any disease or condition. In boys however, it is more likely to be associated with an underlying medical problems • It may be treated by GnRH 2. Delayed puberty • Puberty is considered delayed when there has been no increase in testicular volume by 14 years of age in boys and no beast development by 13 and a half years of age in girls • Constitutional delay that run in families affect both growth and achievement of puberty is much more common in boys than in girls • Chronic medical conditions, such as diabetes or cystic fibrosis, may also cause the delayed onset of puberty. Genetic conditions, problems with pituitary/ thyroid glands, problems with the ovaries/ testes and malnutrition are the other causes of delayed puberty • Many girls who exercises strenuously have very little body fat and also experience a delay in the onset of puberty 3. Others: • Acne • Gynecomastia • • • • • • Anemia STDs Scoliosis Myopia Musculoskeletal injuries Dysfunctional uterine bleeding

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