Talk:Endocrine - Gonad Development

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Cite this page: Hill, M.A. (2021, May 14) Embryology Endocrine - Gonad Development. Retrieved from


Transcriptional activity of oestrogen receptors in the course of embryo development

J Endocrinol. 2018 Sep;238(3):165-176. doi: 10.1530/JOE-18-0003.

Della Torre S1,2, Rando G1,2, Meda C1,2, Ciana P3, Ottobrini L4, Maggi A5,2.


Oestrogens are well-known proliferation and differentiation factors that play an essential role in the correct development of sex-related organs and behaviour in mammals. With the use of the ERE-Luc reporter mouse model, we show herein that throughout mouse development, oestrogen receptors (ERs) are active starting from day 12 post conception. Most interestingly, we show that prenatal luciferase expression in each organ is proportionally different in relation to the germ layer of the origin. The luciferase content is highest in ectoderm-derived organs (such as brain and skin) and is lowest in endoderm-derived organs (such as liver, lung, thymus and intestine). Consistent with the testosterone surge occurring in male mice at the end of pregnancy, in the first 2 days after birth, we observed a significant increase in the luciferase content in several organs, including the liver, bone, gonads and hindbrain. The results of the present study show a widespread transcriptional activity of ERs in developing embryos, pointing to the potential contribution of these receptors in the development of non-reproductive as well as reproductive organs. Consequently, the findings reported here might be relevant in explaining the significant differences in male and female physiopathology reported by a growing number of studies and may underline the necessity for more systematic analyses aimed at the identification of the prenatal effects of drugs interfering with ER signalling, such as aromatase inhibitors or endocrine disrupter chemicals. KEYWORDS: embryo development; oestrogen receptors; reporter mice; sex differences; transcriptional activity




Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

Proc Natl Acad Sci U S A. 2016 Feb 29. pii: 201519395. [Epub ahead of print]

Li X1, Wang Z2, Jiang Z3, Guo J4, Zhang Y3, Li C5, Chung J5, Folmer J5, Liu J5, Lian Q6, Ge R6, Zirkin BR5, Chen H7.


Testicular Leydig cells are the primary source of testosterone in males. Adult Leydig cells have been shown to arise from stem cells present in the neonatal testis. Once established, adult Leydig cells turn over only slowly during adult life, but when these cells are eliminated experimentally from the adult testis, new Leydig cells rapidly reappear. As in the neonatal testis, stem cells in the adult testis are presumed to be the source of the new Leydig cells. As yet, the mechanisms involved in regulating the proliferation and differentiation of these stem cells remain unknown. We developed a unique in vitro system of cultured seminiferous tubules to assess the ability of factors from the seminiferous tubules to regulate the proliferation of the tubule-associated stem cells, and their subsequent entry into the Leydig cell lineage. The proliferation of the stem Leydig cells was stimulated by paracrine factors including Desert hedgehog (DHH), basic fibroblast growth factor (FGF2), platelet-derived growth factor (PDGF), and activin. Suppression of proliferation occurred with transforming growth factor β (TGF-β). The differentiation of the stem cells was regulated positively by DHH, lithium- induced signaling, and activin, and negatively by TGF-β, PDGFBB, and FGF2. DHH functioned as a commitment factor, inducing the transition of stem cells to the progenitor stage and thus into the Leydig cell lineage. Additionally, CD90 (Thy1) was found to be a unique stem cell surface marker that was used to obtain purified stem cells by flow cytometry. KEYWORDS: CD90; DHH; Leydig cell; stem cell; testosterone PMID 26929346


Fetal Testosterone Influences Sexually Dimorphic Gray Matter in the Human Brain

J Neurosci. 2012 Jan 11;32(2):674-680.

Lombardo MV, Ashwin E, Auyeung B, Chakrabarti B, Taylor K, Hackett G, Bullmore ET, Baron-Cohen S. Source Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge CB2 8AH, United Kingdom, Department of Psychology, University of Bath, Bath BA2 7AY, United Kingdom, Centre for Integrative Neuroscience and Neurodynamics, School of Psychology and Clinical Language Sciences, University of Reading, Reading RG6 6AH, United Kingdom, Department of Clinical Biochemistry, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom, Department of Fetal Medicine, Rosie Maternity Hospital, Cambridge CB2 0SW, United Kingdom, and Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Cambridge CB2 0SZ, United Kingdom. Abstract In nonhuman species, testosterone is known to have permanent organizing effects early in life that predict later expression of sex differences in brain and behavior. However, in humans, it is still unknown whether such mechanisms have organizing effects on neural sexual dimorphism. In human males, we show that variation in fetal testosterone (FT) predicts later local gray matter volume of specific brain regions in a direction that is congruent with sexual dimorphism observed in a large independent sample of age-matched males and females from the NIH Pediatric MRI Data Repository. Right temporoparietal junction/posterior superior temporal sulcus (RTPJ/pSTS), planum temporale/parietal operculum (PT/PO), and posterior lateral orbitofrontal cortex (plOFC) had local gray matter volume that was both sexually dimorphic and predicted in a congruent direction by FT. That is, gray matter volume in RTPJ/pSTS was greater for males compared to females and was positively predicted by FT. Conversely, gray matter volume in PT/PO and plOFC was greater in females compared to males and was negatively predicted by FT. Subregions of both amygdala and hypothalamus were also sexually dimorphic in the direction of Male > Female, but were not predicted by FT. However, FT positively predicted gray matter volume of a non-sexually dimorphic subregion of the amygdala. These results bridge a long-standing gap between human and nonhuman species by showing that FT acts as an organizing mechanism for the development of regional sexual dimorphism in the human brain.

PMID 22238103

A crosstalk between bone and gonads

Ann N Y Acad Sci. 2012 Jan 12. doi: 10.1111/j.1749-6632.2011.06360.x. [Epub ahead of print]

Oury F. Source Department of Genetics and Development, Columbia University, New York, New York. Abstract The sex steroid hormones testosterone and estrogen are essential determinants not only of reproductive functions but also for bone growth and the maintenance of skeletal integrity. The importance of this latter form of regulation is best exemplified by the fact that gonadal failure triggers bone loss in both genders and causes osteoporosis in postmenauposal women. Traditionally, bone physiology is studied with the view that the skeleton is simply a recipient of hormonal inputs. However, a richer picture of bone physiology has recently emerged, and it is now clear that the skeleton is an endocrine organ itself. This is particularly relevant to the interplay between bone and gonads because genetics and biochemical evidence have established that bone, via the osteoblast-derived hormone osteocalcin, promotes testosterone biosynthesis. This review will present the mechanism of action of osteocalcin and will discuss the implications of this novel regulation. © 2012 New York Academy of Sciences.

PMID 22239174


Organizational effects of fetal testosterone on human corpus callosum size and asymmetry

Psychoneuroendocrinology. 2010 Jan;35(1):122-32.

Chura LR, Lombardo MV, Ashwin E, Auyeung B, Chakrabarti B, Bullmore ET, Baron-Cohen S. Source Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, UK. Abstract Previous theory and research in animals has identified the critical role that fetal testosterone (FT) plays in organizing sexually dimorphic brain development. However, to date there are no studies in humans directly testing the organizational effects of FT on structural brain development. In the current study we investigated the effects of FT on corpus callosum size and asymmetry. High-resolution structural magnetic resonance images (MRI) of the brain were obtained on 28 8-11-year-old boys whose exposure to FT had been previously measured in utero via amniocentesis conducted during the second trimester. Although there was no relationship between FT and midsaggital corpus callosum size, increasing FT was significantly related to increasing rightward asymmetry (e.g., Right>Left) of a posterior subsection of the callosum, the isthmus, that projects mainly to parietal and superior temporal areas. This potential organizational effect of FT on rightward callosal asymmetry may be working through enhancing the neuroprotective effects of FT and result in an asymmetric distribution of callosal axons. We suggest that this possible organizational effect of FT on callosal asymmetry may also play a role in shaping sexual dimorphism in functional and structural brain development, cognition, and behavior. PMID 19833443

  1. Della Torre S, Rando G, Meda C, Ciana P, Ottobrini L & Maggi A. (2018). Transcriptional activity of oestrogen receptors in the course of embryo development. J. Endocrinol. , 238, 165-176. PMID: 30012715 DOI.