Skeletal sexual dimorphism: relative contribution of sex steroids, GH–IGF1, and mechanical loading

Callewaert, Filip; Sinnesael, Mieke; Gielen, Evelien; Boonen, Steven; Vanderschueren, Dirk

doi:10.1677/joe-10-0209

Cited by 195 publications

(168 citation statements)

References 69 publications

(59 reference statements)

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“…Sexual dimorphism is largely the outcome of the sex-biased expression of autosomal genes, which in turn are regulated by sex-specific hormone levels and/or differential hormone receptor sensitivity (26,27,42). In mice, for example, testicular-feminized males (i.e., males lacking androgen receptors) and gonadectomized males develop female-like pelvic morphologies, whereas experimental administration of androgens to females induces male-like morphologies (28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%

“…In humans, direct evidence for hormone-mediated sex-specific bone remodeling patterns of the pelvis is not yet available. Nevertheless, studies on long bone morphology indicate that sexual skeletal dimorphism develops via complex interactions between sex-specific steroid hormone levels, sex-biased gene expression, and gender differences in sensitivity to bone-loading conditions and to hormones such as the growth hormone/insulin-like growth factor 1 (IGF1) axis (42)(43)(44)(45).…”

Section: Discussionmentioning

confidence: 99%

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Developmental evidence for obstetric adaptation of the human female pelvis

Huseynov

Zollikofer

Coudyzer

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

163

143

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The bony pelvis of adult humans exhibits marked sexual dimorphism, which is traditionally interpreted in the framework of the "obstetrical dilemma" hypothesis: Giving birth to large-brained/ large-bodied babies requires a wide pelvis, whereas efficient bipedal locomotion requires a narrow pelvis. This hypothesis has been challenged recently on biomechanical, metabolic, and biocultural grounds, so that it remains unclear which factors are responsible for sex-specific differences in adult pelvic morphology. Here we address this issue from a developmental perspective. We use methods of biomedical imaging and geometric morphometrics to analyze changes in pelvic morphology from late fetal stages to adulthood in a knownage/known-sex forensic/clinical sample. Results show that, until puberty, female and male pelves exhibit only moderate sexual dimorphism and follow largely similar developmental trajectories. With the onset of puberty, however, the female trajectory diverges substantially from the common course, resulting in rapid expansion of obstetrically relevant pelvic dimensions up to the age of 25-30 y. From 40 y onward females resume a mode of pelvic development similar to males, resulting in significant reduction of obstetric dimensions. This complex developmental trajectory is likely linked to the pubertal rise and premenopausal fall of estradiol levels and results in the obstetrically most adequate pelvic morphology during the time of maximum female fertility. The evidence that hormones mediate female pelvic development and morphology supports the view that solutions of the obstetrical dilemma depend not only on selection and adaptation but also on developmental plasticity as a response to ecological/nutritional factors during a female's lifetime.pelvis | development | evolution | obstetrical dilemma | sex steroids

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Developmental evidence for obstetric adaptation of the human female pelvis

Huseynov

Zollikofer

Coudyzer

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

163

143

View full text Add to dashboard Cite

show abstract

“…However, to systematically address the sexually dimorphic skeletal phenotype in these mice, studies should be conducted comparing estrogen-replete and estrogen-deficient mice. Importantly, gender-specific differences in bone are a result of numerous systemic factors, thus estrogen signaling alone is unlikely to fully account for this discrepancy (Callewaert et al, 2010a;Manolagas et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Defective signaling, osteoblastogenesis and bone remodeling in a mouse model of connexin 43 C-terminal truncation

Moorer

Hebert

Tomlinson

et al. 2017

Journal of Cell Science

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In skeletal tissue, loss or mutation of the gap junction protein connexin 43 (Cx43, also known as GJA1) in cells of the osteoblast lineage leads to a profound cortical bone phenotype and defective tissue remodeling. There is mounting evidence in bone cells that the C-terminus (CT) of Cx43 is a docking platform for signaling effectors and is required for efficient downstream signaling. Here, we examined this function, using a mouse model of Cx43 CT-truncation (Gja1 K258Stop). Relative to Gja1 +/− controls, male Gja1 −/K258Stop mice have a cortical bone phenotype that is remarkably similar to those reported for deletion of the entire Cx43 gene in osteoblasts. Furthermore, we show that the Cx43 CT binds several signaling proteins that are required for optimal osteoblast function, including PKCδ, ERK1 and ERK2 (ERK1/2, also known as MAPK3 and MAPK1, respectively) and β-catenin. Deletion of the Cx43 CT domain affects these signaling cascades, impacting osteoblast proliferation, differentiation, and collagen processing and organization. These data imply that, at least in bone, Cx43 gap junctions not only exchange signals, but also recruit the appropriate effector molecules to the Cx43 CT in order to efficiently activate signaling cascades that affect cell function and bone acquisition.

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“…Skeleton sexual dimorphism is generally attributed to sex steroids such as estradiol (E 2 ), but also to growth hormone, insulin-like growth factor, and mechanical sensitivity to loading (Callewaert et al 2010). Gender differences in lipoprotein metabolism have also been evidenced (for a review, Knopp et al (2005)), but it is unknown if and how this affects bone.…”

Section: Introductionmentioning

confidence: 99%

Gender- and region-specific alterations in bone metabolism in Scarb1-null female mice

Martineau

Martin-Falstrault

Brissette

et al. 2014

Journal of Endocrinology

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A positive correlation between plasma levels of HDL and bone mass has been reported by epidemiological studies. As scavenger receptor class B, type I (SR-BI), the gene product of Scarb1, is known to regulate HDL metabolism, we recently characterized bone metabolism in Scarb1-null mice. These mice display high femoral bone mass associated with enhanced bone formation. As gender differences have been reported in HDL metabolism and SR-BI function, we investigated gender-specific bone alterations in Scarb1-null mice by microtomography and histology. We found 16% greater relative bone volume and 39% higher bone formation rate in the vertebrae from 2-month-old Scarb1-null females. No such alteration was seen in males, indicating gender-and region-specific differences in skeletal phenotype. Total and HDL-associated cholesterol levels, as well as ACTH plasma levels, were increased in both Scarb1-null genders, the latter being concurrent to impaired corticosterone response to fasting. Plasma levels of estradiol did not differ between null and WT females, suggesting that the estrogen metabolism alteration is not relevant to the higher vertebral bone mass in female Scarb1-null mice. Constitutively, high plasma levels of leptin along with 2.5-fold increase in its expression in white adipose tissue were measured in female Scarb1-null mice only. In vitro exposure of bone marrow stromal cells to ACTH and leptin promoted osteoblast differentiation as evidenced by increased gene expression of osterix and collagen type I alpha. Our results suggest that hyperleptinemia may account for the gender-specific high bone mass seen in the vertebrae of female Scarb1-null mice.

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Skeletal sexual dimorphism: relative contribution of sex steroids, GH–IGF1, and mechanical loading

Cited by 195 publications

References 69 publications

Developmental evidence for obstetric adaptation of the human female pelvis

Developmental evidence for obstetric adaptation of the human female pelvis

Defective signaling, osteoblastogenesis and bone remodeling in a mouse model of connexin 43 C-terminal truncation

Gender- and region-specific alterations in bone metabolism in Scarb1-null female mice

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