Estrogen, Progesterone and Testosterone Receptors in Human Fetal Cartilaginous Tissue: Immunohistochemical Studies

Abstract

Computerized image analysis was used to study the distribution in cartilage of receptors to estrogen, progesterone, and testosterone during human fetal development. We have examined three histologically distinct cell groups (hypertrophic, proliferating, and reserve zones) in long bones, vertebrae, and trachea from 19 fetuses. Comparisons were made across gender and gestational age. Contrasting with controls, we examined the density of receptors, the size of the nuclear area in which the receptors were detected, the number of hormone receptor-bearing cells, and the total receptor quantity per sample. We found that estrogen, progesterone, and testosterone receptors were detected in the nuclei of all cell types, in both female and male embryonic cartilaginous tissue. Gender differences were small and inconsistent. Changes associated with gestational age depicted a pattern of hormone receptor manifestation, shifting from the immature cell types to more differentiated cells. This was evident from the receptor densities and from the cellular area in which receptors were sighted. These dynamics are accompanied by a general increase in receptor content per sample, brought about by the concomitant increase in receptor containing area size and cell number. The increase in receptor levels seems to reflect the maturation and growth of the fetal skeleton.

Female hormone receptors are differentially expressed in mouse fibrocartilages

“…The localization of these hormone receptors in developing endochondral bone, mature cartilage and, as shown by the present studies, in fibrocartilage attests to the importance of the receptors and their respective hormones in cartilage development and physiology 12,14,42,43. It is well known that these hormones regulate the proliferation, differentiation, maturation and programmed cell death of chondrocytes 6,39-41.…”

“…Thus, while chondrocytes within the knee articular cartilage have been shown to be positive for estrogen and progesterone receptors,14,15 those from thyroid cartilage of male and female subjects did not react with ER-α and PR antibodies 13. These and other studies also show differences in distribution of mRNA and proteins for ERs and PR in articular cartilages and in chondrocytes at various stages of differentiation in developing endochondral bone 42,43. Together, these studies highlight the need for concurrent comparative analysis of receptor levels in cartilages in different joints, as performed in the present study.…”

Interpretation of skeletal variations for human risk assessment: delayed ossification and wavy ribs

“…In vivo, treatment of mice on GD 9-15 with the potent estrogen receptor agonist, DES, increased the bone density of female offspring when they were examined in adulthood (Migliaccio et al, 1996). Receptors for estrogen, testosterone, and progesterone have been found in rodent fetuses (Ben-Hur et al, 1997). Consistent with the bone-stimulating role of estrogens is evidence from humans with estrogen deficiency syndromes caused by mutations in the estrogen receptor or aromatase (converts androgens to estrogens) genes.…”

Androgens and bone

“…These receptors are expressed in all layers of the human growth plate at different ages [12], but only in the proliferative and early hypertrophic chondrocytes in sexually mature rats, and only in prehypertrophic chondrocytes in older rats [13]. No differences have been detected in androgen receptor expression in growth plate chondrocytes from human males or females [10,12], whereas male rats have increased androgen receptor expression in the growth plate and metaphyseal bone during sexual maturation compared to female rats [13]. In light of these findings, it is likely that androgens directly influence longitudinal bone growth during early puberty and epiphyseal growth plate closure in later puberty.…”