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Hormonal Mechanisms in the Onset of Puberty RONALD S

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Postgrad Med J: first published as 10.1136/pgmj.51.594.200 on 1 April 1975. Downloaded from Postgraduate Medical Journal (April 1975) 51, 200-208. Hormonal mechanisms in the onset of puberty RONALD S. SWERDLOFF* WILLIAM D. ODELL M.D. M.D., Ph.D. Division of Endocrinology, Harbor General Hospital Campus, U.C.L.A. School of Medicine, U.S.A. Summary Sexual maturation is associated with increasing levels I I II >Apex of sex steroids. These steroidal events are the result of strength spurt complex changes that occur at several functional levels including the hypothalamus, pituitary, gonad and Height spurt I adrenal gland. These changes, as outlined in Table 3, 10-5 - 16 13 5 - 17 5 are often interrelated. Penis While considerable progress has been made in our 10 5-14-5 12'-5-16-5 understanding of the hormonal events associated with Testis sexual maturation, many important questions remain 9 5 - 13 5 13-5- 17 unanswered. Further intensive investigation will be Gonadal rating 2'3 M4 5 required before we have a lucid understanding of the physiological basis of the sequence of hormonal events Pubic hair 21llI1IIIIlII3IIIIIII4lIlIIIIlII5llIlIIiIiIii by copyright. which occur during the pubertal process. 8 9 10 11 12 13 14 15 16 17 Age (years) Sexual maturation FIG. 2. Sequence of development of physical changes The transformation of a sexually immature child associated with puberty in boys. The numbers 2-5 refer into an adult capable of normal reproductive com- to the Tanner stages of pubic hair and genital develop- petence is the result of a complex series of hormonal ment (with permission from Marshall and Tanner, 1970). events. The sequence of development of the many physical changes associated with puberty have been carefully documented by Marshall and Tanner (1969, 1970). The physical changes which occur over a time http://pmj.bmj.com/ span of several years have been subdivided into several stages for simpler discussion of chronology, relationship to hormonal changes and diagnosis of abnormal maturational development. The widely Height spurt I U used classification system of Marshall and Tanner 9 5 - 14 5 (1969, 1970) actually represents two classifications based on separate but Menarche U interrelated events, e.g. pubic on September 30, 2021 by guest. Protected 10-16 5 hair and genital development in the male. Figures 1 and 2 represent the chronology of these stages in Breast 2Q &3 #4 5 boys and girls during the past two decades in England. 8-13 13-18 Efforts have been made by several groups to develop Pubic hair 211111111311111114 11111111111115 a composite staging system to allow for easier correlation with hormonal events (e.g. Winter and e 9 10 11 12 13 14 15 16 17 Faiman, 1972a). Similar classification systems used in our 1 Age (years) clinics are presented in Table and 2. The ages of children in whom these pubertal stages are FIG. 1. Sequence of development of physical changes observed differ depending on the geographical and associated with puberty in girls. The numbers 2-5 refer to the Tanner stages of pubic hair and breast develop- nutritional environment of the children. The latter ment (with permission from Marshall and Tanner, 1970). factor has been proposed as the explanation for the trend toward the earlier development of menarche * Recipient of USPHS Career Development Award #5 (Tanner, 1962; Frisch, 1972) observed over the past K04 HD 70436-02. century. Postgrad Med J: first published as 10.1136/pgmj.51.594.200 on 1 April 1975. Downloaded from Hormonal mechanisms in the onset ofpuberty 201 TABLE 1. Composite stages of sexual development in possibly prolactin). Secretion of LH and FSH males depends on the stimulatory effects of the hypo- thalamic releasing hormone, GnRH (Schally, Kastin Stage Description and Arimura, 1971). GnRH secretion is regulated by P-1 Preadolescent; largest testes diameter < 2-4 hypothalamic monoamines such as norepinephrine, cm; no pubic hair or penile enlargement dopamine and serotonin (Kamberi, Mical and P-2 Sparse pubic hair, mainly at base of penis; Porter, 1971). Higher CNS structures undoubtedly testis diameter 2-43-2 cm; scrotal skin reddened; little penile enlargement influence the production of the latter substances. P-3 Pubic hair darker, coarser, but limited in dis- Both hypothalamic and pituitary function are tribution; early penis enlargement; sparse influenced by the gonads. In the male, testosterone, axillary hair; testes diameter 3-3-40 cm; dihydrotestosterone, oestradiol and perhaps other scrotal skin darker gonadal substances act via negative feedback to P-4 Adult pubic hair; moderate axillary hair; inhibit the secretion of LH and FSH (Swerdloff et al., testis diameter 4 14-5 cm 1973; Walsh, Swerdloff and Odell, 1973a, b). It is P-5 Adult secondary characteristics; testis dia- meter than 4-5 cm likely that this negative feedback occurs both at the greater hypothalamic level (inhibiting the secretion of Adapted from Marshall and Tanner (1970) and Winter GnRH) (Smith and Davidson, 1967) and at the and Faiman (1972a). pituitary level (Wollessen et al., 1974; Vera, Swerd- loff and Odell, 1974) inhibiting the effects of GnRH TABLE 2. Composite stages of sexual development in on LH and FSH secretion. Thus, in a normal adult females male, castration results in increased secretion of LH Stage Description and FSH owing to the absence of the inhibitory effects of gonadal steroids. Treatment of such a P-1 Preadolescent person with androgens and/or oestrogens results in a P-2 Breast budding; early labial hair growth return of these gonadotrophins towards normal. The by copyright. P-3 Increased breast size with palpable glandular for the male is in 3. tissue; no separating of breast contours; feedback system depicted Fig. moderately dark coarser labial hair over mons pubis Extrohypothalamic Environment P-4 Further enlargement of breasts with projec- CNS tion of areola above breast plane; lateral spread of pubic hair P-5 Adult breast size and pubic hair distribution + Cyclic | Tonic area area Adapted from Marshall and Tanner (1969). + Catecholomines http://pmj.bmj.com/ events in puberty GNRH - Metabolic Hormonal effects With the exception of gonadal size, most of the visible changes associated with puberty in both sexes Pituitary are due to increased production of steroid hormones. FSH LH These hormones are secreted directly by the gonads and adrenals or are converted from precursor steroids Testis secreted by the adrenals. In the male, pubic, axillary on September 30, 2021 by guest. Protected and facial hair, phallic enlargement, change in . muscle mass and epiphyseal closure all result from sExtrogonodal sourcesT+DHT;E2+ X Degrsdative increasing concentrations of androgens. These ~~~~~~systems androgens are predominantly produced by the FIG. 3. Hypothalamic-pituitary-gonadal feedback system but a small contribution is due to the direct of the male. The extragonadal sources of androgen re- testes, ferred to include androgens and androgen precursors secretion of weak androgens and androgen pre- produced by the adrenal glands. The testis directly cursors from the adrenal glands. In the female, secretes testosterone, dehydrotestosterone and oestradiol. breast development, female fat distribution, vaginal Other substances have been postulated to be secreted by and uterine development, linear growth velocity and the testes which are believed to have an influence on FSH secretion. Such a substance referred to as )X' in the skeletal maturation are the result of increasing diagram has been given various names including oestrogen secretion by the ovary. The mechanism by 'inhibin'. which increased production of adrenal androgens (adrenarche) occurs at puberty is incompletely In the female (as in the male), a tonic negative understood. The gonads are under the control of the feedback system exists and ovarian steroids (oestro- pituitary gonadotrophic hormones (LH, ESH and gen and progesterone) inhibit LH and FSH secretion Postgrad Med J: first published as 10.1136/pgmj.51.594.200 on 1 April 1975. Downloaded from 202 R. S. Swerdloffand W. D. Odell (Odell and Swerdloff, 1968; Swerdloff and Odell, Folliculor Luteol - 1969). This inhibitory influence probably occurs at phIphasee pphasee I both hypothalamic and pituitary levels. In addition, the female has a positive feedback system (Fig. 4) by which oestrogens stimulate LH secretion (Swerd- loff and Odell, 1969; Yenn, 1971). Progestogens may synergize with oestrogens in this stimulatory action on LH secretion and they may be necessary for E stimulation at midcycle (Odell and Swerdloff, 1968; Swerdloff, Jacobs and Odell, 1972a). This stimulatory action ofgonadal steroids results in the pre-ovulatory surge of LH and FSH observed at midcycle. 300 - E 200 100 -E2 60 Degradative , systems - Metabolic effects by copyright. E 40r E 15 - LH j1 FIG. 4. Hypothalamic-pituitary-gonadal feedback system of the female. 10 , serum Figure 5 depicts the cyclic changes of LH, http://pmj.bmj.com/ FSH, oestradiol and progesterone during a normal E menstrual cycle (Abraham et al., 1971). The follow- F1 ing sequence of events occurs. FSH rises early in the 51 cycle and stimulates growth of the ovarian follicle. The growing follicle secretes increasing amounts of 4 10 14 20 28 oestradiol (and 17-a-hydroxy-progesterone). When Davs a critical the oestradiol concentration reaches level, FIG. 5. Daily serum LH, FSH, oestradiol-17B and pro- it triggers release of large quantities of LH and FSH. gesterone concentrations in a normal menstrual cycle on September 30, 2021 by guest. Protected Ovulation then occurs and a corpus luteum develops. (with permission from Abraham et al., 1971). Progesterone concentrations, which begin to rise just before the midcycle LH peak, are markedly increased Gonadotrophins during the luteal phase. The elevated concentrations Until recently, most physicians believed that the of oestradiol and progesterone act via the negative prepubertal child was not able to secrete gonado- feedback system to inhibit secretion of LH and FSH.
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