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The endocrine role of estrogens on human male skeleton.

Rochira V, Kara E, Carani C - Int J Endocrinol (2015)

Bottom Line: At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached.This threshold should be better identified in-between the ranges of 15 and 25 pg/mL.Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men.

View Article: PubMed Central - PubMed

Affiliation: Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via P. Giardini 1355, 41126 Modena, Italy ; Azienda USL di Modena, Nuovo Ospedale Civile Sant'Agostino Estense (NOCSAE), Via P. Giardini 1355, 41126 Modena, Italy.

ABSTRACT
Before the characterization of human and animal models of estrogen deficiency, estrogen action was confined in the context of the female bone. These interesting models uncovered a wide spectrum of unexpected estrogen actions on bone in males, allowing the formulation of an estrogen-centric theory useful to explain how sex steroids act on bone in men. Most of the principal physiological events that take place in the developing and mature male bone are now considered to be under the control of estrogen. Estrogen determines the acceleration of bone elongation at puberty, epiphyseal closure, harmonic skeletal proportions, the achievement of peak bone mass, and the maintenance of bone mass. Furthermore, it seems to crosstalk with androgen even in the determination of bone size, a more androgen-dependent phenomenon. At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached. The same mechanism based on a critical threshold of serum estradiol seems to operate in men during adulthood for bone mass maintenance via the modulation of bone formation and resorption in men. This threshold should be better identified in-between the ranges of 15 and 25 pg/mL. Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men.

No MeSH data available.


Related in: MedlinePlus

Direct and indirect effects of increasing circulating estrogens and their depletion on the growth plate (a), and effects of estrogen deprivation on bone elongation and epiphyseal status (b). AR: androgen receptor; E1: estrone; E2: estradiol; T: testosterone; ER-α: estrogen receptor alpha; ER-β: estrogen receptor beta; GPR30: membranous-G-protein-coupled estrogen receptor.
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fig1: Direct and indirect effects of increasing circulating estrogens and their depletion on the growth plate (a), and effects of estrogen deprivation on bone elongation and epiphyseal status (b). AR: androgen receptor; E1: estrone; E2: estradiol; T: testosterone; ER-α: estrogen receptor alpha; ER-β: estrogen receptor beta; GPR30: membranous-G-protein-coupled estrogen receptor.

Mentions: Later on, these findings opened the way to studies investigating the role of estrogens on bone growth and maturation not only in the context of congenital estrogen defects but also in normal boys. Serum E2 was found to increase simultaneously with T levels during puberty in boys and to correlate directly with chronological and skeletal age, height, weight, and pubertal stages, thus confirming the crucial role of estrogens on bone physiology at puberty even in the male [19, 21] (Table 1). In particular, estrogens seem to have a dose-dependent effect on growth plates [21, 47]: actually low doses of E2 stimulate ulnar growth in boys [33], while higher doses lead to an inhibition of this process of growth [20]. Recently, circulating serum E2 measured by LC/MS/MS resulted directly related to both the genital Tanner stage and the skeletal maturation in pubertal boys [18]. In addition, serum E2 was significantly higher and bone age more advanced in obese boys compared with healthy boys at the same pubertal stage [48]. The excess of adipose tissue in obese boys probably accounts for increased aromatization of androgens into estrogens and for the advancement of bone age due to the higher amounts of circulating estrogens [18, 48]. This result is in line with the well-known gender difference in the progression of skeletal maturation, which is more rapid in women than in men and parallels gender differences in the way serum E2 increases throughout puberty [19, 20, 33, 35]. At the beginning of puberty, when circulating E2 is low, the prevailing effect of E2 consists in the promotion of chondrocytes proliferation within the growth plate, resulting in growth plate lengthening and accelerated bone elongation (Figure 1) (Table 1). This corresponds to the increase of height velocity occurring during pubertal growth spurt that is postulated to be under estrogen control (Table 1) [21, 40, 47]. As puberty goes on, the rise in serum T ensures high E2 circulating levels, typical of late puberty; E2 inhibits chondrocyte proliferation and stimulate chondrocyte differentiation, thus inducing the progressive ossification of the growth plate and its final disappearance (Figure 1). At present, the amount of E2 required for shifting from the increase in length of the growth plate to its growth deceleration and final closure of the growth plate line is not known in detail. Data available in literature clearly show that no difference in serum T is present between men with idiopathic hypogonadotropic hypogonadism with fused epiphyses compared to those with unfused epiphyses [30], but no data are available in literature on serum estrogens in these rare conditions. This implies that androgen is not involved in the process of shifting from growth plate elongation to progressive growth plate thinning and final disappearance (Table 1).


The endocrine role of estrogens on human male skeleton.

Rochira V, Kara E, Carani C - Int J Endocrinol (2015)

Direct and indirect effects of increasing circulating estrogens and their depletion on the growth plate (a), and effects of estrogen deprivation on bone elongation and epiphyseal status (b). AR: androgen receptor; E1: estrone; E2: estradiol; T: testosterone; ER-α: estrogen receptor alpha; ER-β: estrogen receptor beta; GPR30: membranous-G-protein-coupled estrogen receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4383300&req=5

fig1: Direct and indirect effects of increasing circulating estrogens and their depletion on the growth plate (a), and effects of estrogen deprivation on bone elongation and epiphyseal status (b). AR: androgen receptor; E1: estrone; E2: estradiol; T: testosterone; ER-α: estrogen receptor alpha; ER-β: estrogen receptor beta; GPR30: membranous-G-protein-coupled estrogen receptor.
Mentions: Later on, these findings opened the way to studies investigating the role of estrogens on bone growth and maturation not only in the context of congenital estrogen defects but also in normal boys. Serum E2 was found to increase simultaneously with T levels during puberty in boys and to correlate directly with chronological and skeletal age, height, weight, and pubertal stages, thus confirming the crucial role of estrogens on bone physiology at puberty even in the male [19, 21] (Table 1). In particular, estrogens seem to have a dose-dependent effect on growth plates [21, 47]: actually low doses of E2 stimulate ulnar growth in boys [33], while higher doses lead to an inhibition of this process of growth [20]. Recently, circulating serum E2 measured by LC/MS/MS resulted directly related to both the genital Tanner stage and the skeletal maturation in pubertal boys [18]. In addition, serum E2 was significantly higher and bone age more advanced in obese boys compared with healthy boys at the same pubertal stage [48]. The excess of adipose tissue in obese boys probably accounts for increased aromatization of androgens into estrogens and for the advancement of bone age due to the higher amounts of circulating estrogens [18, 48]. This result is in line with the well-known gender difference in the progression of skeletal maturation, which is more rapid in women than in men and parallels gender differences in the way serum E2 increases throughout puberty [19, 20, 33, 35]. At the beginning of puberty, when circulating E2 is low, the prevailing effect of E2 consists in the promotion of chondrocytes proliferation within the growth plate, resulting in growth plate lengthening and accelerated bone elongation (Figure 1) (Table 1). This corresponds to the increase of height velocity occurring during pubertal growth spurt that is postulated to be under estrogen control (Table 1) [21, 40, 47]. As puberty goes on, the rise in serum T ensures high E2 circulating levels, typical of late puberty; E2 inhibits chondrocyte proliferation and stimulate chondrocyte differentiation, thus inducing the progressive ossification of the growth plate and its final disappearance (Figure 1). At present, the amount of E2 required for shifting from the increase in length of the growth plate to its growth deceleration and final closure of the growth plate line is not known in detail. Data available in literature clearly show that no difference in serum T is present between men with idiopathic hypogonadotropic hypogonadism with fused epiphyses compared to those with unfused epiphyses [30], but no data are available in literature on serum estrogens in these rare conditions. This implies that androgen is not involved in the process of shifting from growth plate elongation to progressive growth plate thinning and final disappearance (Table 1).

Bottom Line: At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached.This threshold should be better identified in-between the ranges of 15 and 25 pg/mL.Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men.

View Article: PubMed Central - PubMed

Affiliation: Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via P. Giardini 1355, 41126 Modena, Italy ; Azienda USL di Modena, Nuovo Ospedale Civile Sant'Agostino Estense (NOCSAE), Via P. Giardini 1355, 41126 Modena, Italy.

ABSTRACT
Before the characterization of human and animal models of estrogen deficiency, estrogen action was confined in the context of the female bone. These interesting models uncovered a wide spectrum of unexpected estrogen actions on bone in males, allowing the formulation of an estrogen-centric theory useful to explain how sex steroids act on bone in men. Most of the principal physiological events that take place in the developing and mature male bone are now considered to be under the control of estrogen. Estrogen determines the acceleration of bone elongation at puberty, epiphyseal closure, harmonic skeletal proportions, the achievement of peak bone mass, and the maintenance of bone mass. Furthermore, it seems to crosstalk with androgen even in the determination of bone size, a more androgen-dependent phenomenon. At puberty, epiphyseal closure and growth arrest occur when a critical number of estrogens is reached. The same mechanism based on a critical threshold of serum estradiol seems to operate in men during adulthood for bone mass maintenance via the modulation of bone formation and resorption in men. This threshold should be better identified in-between the ranges of 15 and 25 pg/mL. Future basic and clinical research will optimize strategies for the management of bone diseases related to estrogen deficiency in men.

No MeSH data available.


Related in: MedlinePlus