Hormonal Control of Puberty

The hormonal regulation of growth becomes increasingly complex just before and with
the onset of puberty. Adequate levels of thyroid hormone and cortisol continue to be
prerequisites for normal growth, but the gonadal steroid hormones now play an increasingly
major role. There is also a dramatic activation of the GH/IGF-I axis. During
adolescence the gonadal steroid hormones and the GH/IGF-I axis continue to
exert independent effects on growth, but the interaction between them underlies the
dramatic alterations in linear growth velocity and body composition, including the regional
distribution of body fat.
Pulsatile gonadotropin secretion occurs at all ages, but puberty is heralded by an increase
in the amplitude of luteinizing hormone (LH) and follicle-stimulating hormone
(FSH) secretion, detectable even before the first external signs of pubertal development
are evident. This stage represents a reawakening of the state of the gonadal axis operative
during the late fetal and very early neonatal stages. Initially, biologically relevant
surges of LH occur predominantly at night, resulting in elevations of gonadal steroid
hormone concentration early in the morning. These then wane during the day as these
small but relevant levels of gonadal steroids reduce the levels of the gonadotropins because
the negative feedback remains operative at the very sensitive prepubertal stage.
With continuing maturation of the HPG axis (i.e., becoming relatively less sensitive to
the negative feedback of the gonadal steroid hormones), enhanced pulsatile LH release
occurs throughout the waking hours as well, resulting in more stable elevations of the
gonadal steroid hormones. The rising levels of these hormones promote the development
of secondary sex characteristics and the changes in body composition and the regional
distribution of body fat noted during pubertal development. Gonadal steroid
Biology of Puberty 21
hormones, primarily estradiol in both genders, also enhance bone mineral accrual and
affect adult height by promoting epiphyseal fusion.
A dramatic activation of the GH/IGF-I axis occurs during early- to midpuberty. The
rise in the mean 24-hour GH levels results from an increase in the maximal GH secretory
rate (pulse amplitude) and in the mass of GH secreted per secretory burst (Veldhuis
et al., 2000). The differential increase in GH secretion between boys and girls at
puberty follows the pattern of change in growth velocity. Girls show a significant rise in
circulating GH levels beginning at Tanner breast stage 2, with the highest levels found
at Tanner breast stage 3–4. An increase occurs later in boys, peaking at Tanner genital
stage 4 (Martha, Gorman, Blizzard, Rogol, & Veldhuis, 1992). During midpuberty the
day-night rhythm is obscured because of a greater rate of rise in secretory amplitude
during the day than the night (Martha et al., 1992). By the time adolescent development
is complete, the levels of GH and IGF-I decrease to nearly prepubertal levels in both
genders.
Clinical observations have shown that both GH and sex steroid hormones must be
present for normal pubertal growth. Individuals with a selective deficiency of either
hormone (e.g., hypogonadotropic hypogonadism or isolated GH deficiency) have an
attenuated pubertal growth spurt (Aynsley-Green, Zachmann, & Prader, 1976; Liu,
Merriam, & Sherins, 1987). Many of the growth-promoting actions of the gonadal
steroid hormones are mediated through the estrogen rather than androgen receptor, either
by direct secretion of estrogen or conversion of androgens to estrogens by peripherally
located aromatase. Individuals with complete androgen insensitivity demonstrate
that androgens are not necessary to support normal adolescent growth or to
achieve pubertal levels of GH and IGF-I if sufficient levels of estrogen are present
(Zachmann et al., 1986). Estrogens are responsible for skeletal maturation and fusion
of the epiphyseal plates.
Adrenarche
Adrenarche refers to the activation of adrenal androgen production from the zona
reticularis. These androgens produce pubic and axillary hair (pubarche) as well as body
odor, oily skin, and acne. Adrenarche stems from a poorly understood activation of the
HPA axis for androgen production, separate and distinct from the usual activation of
the HPA axis for cortisol production. There is a progressive increase in circulating levels
of dehydroepiandrosterone (DHEA) and its sulfated form (DHEAS) in both boys
and girls beginning by age 7 or 8 years and continuing throughout early adulthood before
declining with advancing age.
The exact mechanism responsible for the onset of adrenarche is controversial, although
recent evidence suggests that adrenocorticotropic hormone (ACTH; Weber,
Clark, Perry, Honour, & Savage, 1997) and/or 3-hydroxysteroid dehydrogenase play a
significant role in the regulation of adrenarche (Gell et al., 1998). Adrenarche only recently
began to be studied in relation to psychological development (Dorn, Hitt, &
Rotenstein, 1999), as discussed later.
Leptin and Puberty
Discovery of the hormone leptin led to the theory that it may be a signal allowing for
the initiation of and progression toward puberty (Mantzoros, Flier, & Rogol, 1997). An
22 Puberty and Psychological Development
alternative perspective is that leptin is implicated in the onset of puberty but may not
be the cause of the onset. Leptin is 16-kDa adipocyte-secreted protein, a product of the
obesity (ob) gene. Serum leptin levels reflect mainly the amount of energy stores but are
also influenced by short-term energy imbalance as well as several cytokines (indices of
immune system function) and hormones. Leptin is implicated in the initiation of puberty,
energy expenditure, normal menstrual cycles, fertility, maintenance of pregnancy,
and nutrition. Specifically, leptin may well be one of the messenger molecules signaling
the adequacy of the fat stores at puberty for reproduction and maintenance of pregnancy
(Kiess et al., 1999). The possible mechanism involves leptin as a hormone that
serves to signal the brain with information on the critical amount of fat stores that are
necessary for luteinizing hormone-releasing hormone (LHRH) secretion and activation
of the HPA axis. Moreover, circadian and ultradian variations of leptin levels are
also associated with minute-to-minute variations of LH and estradiol in normal women
(Mantzoros, 2000). The mechanisms by which leptin regulates body weight, adiposity,
and the hormones that increase at puberty (e.g., testosterone and estrogen) are not yet
known.
Leptin is higher in girls than in boys controlling for adiposity (Blum et al., 1997). At
the initiation of puberty, circulating leptin concentrations diverge in boys and girls. In
boys, leptin concentrations increase and then markedly decrease to prepubertal concentration
levels in late puberty. In contrast, in girls there are increasing concentrations
at puberty (Roemmich & Rogol, 1999). The increase in leptin is believed to result from
different alterations in the regional distribution of body fat in boys and girls at puberty.
Overall, sex differences in leptin concentrations are accountable to differences in the
amounts of subcutaneous fat in girls and greater androgen concentrations in boys
(Roemmich, Clark, Berr, et al., 1998). The biological effects of leptin in adult humans
are still to be determined, but reports show that congenital leptin deficiency leads to hyperphagia
and excessive weight gain from early infancy onward as well as failure of pubertal
onset in adolescence (Ong, Ahmed, & Dunger, 1999). Leptin concentrations
have not yet been examined in relation to behavior changes at puberty, but leptin provides
a promising biological probe for understanding pubertal processes and problems
of body image.