Control of human luteal steroidogenesis

Devoto, Luigi; Kohen, Paulina; Vega, Margarita; Castro, Olga; González, Ricardo R.; Retamales, Iván; Carvallo, Pilar; Christenson, Lane K.; Strauss, Jerome F.

doi:10.1016/s0303-7207(01)00654-2

Cited by 75 publications

(44 citation statements)

References 21 publications

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“…The corpus luteum is associated with intense angiogenesis (Reynolds et al 2000, Wulff et al 2001) followed by vascular regression. As oestradiol is produced by the granulosa-lutein cells (Devoto et al 2002b) of the corpus luteum, with receptors on endothelial cells, it may have potential effects on endothelial cell function. It is not known whether oestradiol has any direct effects, but it is notable that molecules based on oestrogen have been shown to have anti-angiogenic properties (Klauber et al 1997, Mooberry 2003, Tinley et al 2003.…”

Section: Discussionmentioning

confidence: 99%

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Expression and regulation of oestrogen receptors in the human corpus luteum

Driesche¹,

Smith²,

Myers³

et al. 2008

Reproduction

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The molecular mechanisms underlying the control of corpus luteum lifespan in women are not fully understood. Oestradiol has various luteolytic, or luteotrophic, functions in some species, and as it is synthesised within the human corpus luteum, it is an excellent candidate molecule to be a paracrine regulator of luteal function. This study aimed to comprehensively investigate the expression, regulation and effects of oestrogen receptors (ER) in human luteal cells. Genomic oestrogen receptors ERa, ERb1 and ERb2 were immunolocalised in human corpora lutea from throughout the luteal phase. mRNA expression was investigated throughout the luteal phase and after luteal rescue with exogenous human chorionic gonadotrophin (hCG). The regulation of ER expression and oestradiol action was investigated in cultures of luteinised granulosa cells. ER subtypes ERb1 and ERb2 were localised throughout the luteal phase to steroidogenic cells in the human corpus luteum and cells of the surrounding stroma. Unlike follicular granulosa cells, steroidogenic cells in the corpus luteum showed minimal ERa immunostaining. The presence of endothelial cells in the granulosa cell layer with ERb1 and ERb2 positive nuclei was noted. ERb1 and ERb2 were differentially regulated across the luteal phase with ERb1 maximally expressed in the mid-luteal phase, while ERb2 expression was maximal in the early luteal phase. In vivo and in vitro, hCG had no long-term effect on ER expression, although in vitro hCG and oestradiol acutely down-regulated ERs. Treatment with oestradiol in vitro down-regulated 11b-hydroxysteroid dehydrogenase type 1 and inhibin bA subunit confirming a functional oestradiol response. These data highlight functional and differentially regulated oestradiol reception in human luteal cells.

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Section: Discussionmentioning

confidence: 99%

“…While progesterone is an attractive paracrine regulatory molecule in the corpus luteum (Vega & Devoto 1997, Stouffer 2003, characterisation of important and clear luteal effects of progesterone has remained elusive (Devoto et al 2002a(Devoto et al , 2002b. The same cannot be said for oestrogen.…”

Section: Introductionmentioning

confidence: 99%

Expression and regulation of oestrogen receptors in the human corpus luteum

Driesche¹,

Smith²,

Myers³

et al. 2008

Reproduction

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“…Khil, H.-S. Jun and H. Kwon, unpublished results). However, we cannot exclude the possibility that hCG, which is a pleiotropic hormone, might also exert its immunosuppressive effects by modulating the level of other reproductive hormones such as progesterone and testosterone [1,33,34] and thereby prevent the development of type 1 diabetes in NOD mice.…”

Section: Cd4mentioning

confidence: 99%

Human chorionic gonadotropin is an immune modulator and can prevent autoimmune diabetes in NOD mice

et al. 2007

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Aims/hypothesis Expression of T helper (Th)1 cytokine mRNA in pregnant women is known to be inversely correlated with serum human chorionic gonadotropin (hCG). Type 1 diabetes is a Th1-mediated autoimmune disease, in which intervention at an early stage of the autoimmune process can prevent disease progression. We hypothesised that immune modulation by treating young NOD mice with hCG may prevent diabetes. Methods Female NOD mice were treated with hCG or recombinant hCG from 3 to 15 weeks of age and the incidence of diabetes and development of insulitis was determined. CD4 + and CD8 + T cell populations, T cell proliferation, cytokine production and CD4 + CD25+ regulatory T cells were examined and adoptive transfer experiments were performed.Results Both purified and recombinant hCG prevented development of diabetes in NOD mice. hCG decreased the proportion and number of CD4 + and CD8 + T cells and inhibited T cell proliferative responses against beta cell antigens. hCG treatment suppressed IFN-γ production, but increased IL-10 and TGF-β production in splenocytes stimulated with anti-CD3 antibody. hCG treatment also suppressed TNF-α production in splenocytes stimulated with lipopolysaccharide. + /CD4 + T cell ratio, thus preventing autoimmune diabetes in NOD mice.

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“…HCG, a pleiotropic hormone, can influence the level of other reproductive hormones (14,15), which in turn could have an immunomodulatory effect. However, there is growing evidence that HCG can also act directly as an immune modulator (8,16), because its receptors are widely distributed in nongonadal tissue, including immune cells (17).…”

Section: Discussionmentioning

confidence: 99%

Human chorionic gonadotropin prevents Sjögren's syndrome–like exocrinopathy in mice

Shigihara

Tzioufas

et al. 2007

Arthritis & Rheumatism

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Objective.Results of recent studies suggest that human chorionic gonadotropin (HCG), a placental glycoprotein hormone required for the maintenance of pregnancy, may have immunomodulatory properties. Primary Sjögren's syndrome (SS), a chronic autoimmune disorder of unknown etiology, affects multiple exocrine glands including the salivary and lacrimal glands. The purpose of the present study was to determine whether HCG could prevent the development of salivary gland exocrinopathy in NOD mice, an experimental model of Sjögren's-like syndrome.Methods. Female NOD mice were treated with HCG from 6 weeks of age to 12 weeks of age. At 14 weeks, tissue samples were evaluated for inflammatory lesions and cytokine messenger RNA by real-time polymerase chain reaction. At 18 weeks, the salivary flow rate was measured.Results. Treatment with HCG resulted in a significant decrease in lymphocyte infiltration and parenchymal cell damage in the submandibular salivary glands. Messenger RNA levels of interferon-␥, tumor necrosis factor ␣, interleukin-1␤, and interleukin-10, as well as inducible nitric oxide synthase and matrix metalloproteinase 9, were significantly decreased. Function studies revealed a marked increase in the salivary flow rate in HCG-treated mice compared with that in phosphate buffered saline-treated mice.Conclusion. In NOD mice, HCG acts as an immune modulator and prevents the development of salivary gland exocrinopathy. These findings suggest that HCG, a naturally occurring reproductive hormone, may be useful in the treatment of Sjögren's syndrome and other human autoimmune diseases.

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Control of human luteal steroidogenesis

Cited by 75 publications

References 21 publications

Expression and regulation of oestrogen receptors in the human corpus luteum

Expression and regulation of oestrogen receptors in the human corpus luteum

Human chorionic gonadotropin is an immune modulator and can prevent autoimmune diabetes in NOD mice

Human chorionic gonadotropin prevents Sjögren's syndrome–like exocrinopathy in mice

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