Analysis of 17β-estradiol (E2) role in the regulation of corpus luteum function in pregnant rats: Involvement of IGFBP5 in the E2-mediated actions

Abstract

BackgroundIn several species, considerably higher levels of estradiol-17 (E2) are synthesized in the CL. E2 has been suggested to participate in the regulation of luteal steroidogenesis and luteal cell morphology. In pregnant rats, several experiments have been carried out to examine the effects of inhibition of luteal E2 synthesis on CL structure and function.MethodsDuring days 12–15 of pregnancy in rats, luteal E2 was inhibited by way of daily oral administration of anastrozole (AI), a selective non-steroidal aromatase inhibitor, and experiments were also performed with E2 replacement i.e. AI+ E2 treatments. Luteal tissues from different treatment groups were subjected to microarray analysis and the differentially expressed genes in E2 treated group were further examined for expression of specific E2 responsive genes. Additional experiments were carried out employing recombinant growth hormone preparation and flutamide, an androgen receptor antagonist, to further address the specificity of E2 effects on the luteal tissue.ResultsMicroarray analysis of CL collected on day 16 of pregnancy post AI and AI+E2 treatments showed significantly lowered cyp19a1 expression, E2 levels and differential expression of a number of genes, and several of them were reversed in E2 replacement studies. From the differentially expressed genes, a number of E2 responsive genes were identified. In CL of AI pregnant rats, non-significant increase in expression of igf1, significant increase in igbp5, igf1r and decrease in expression of Erα were observed. In liver of AI treated rats, igf1 expression did not increase, but GH treatment significantly increased expression that was further increased with AI treatment. In CL of GH and AI+GH treated rats, expression of igfbp5 was higher. Administration of flutamide during days 12–15 of pregnancy resulted in non-significant increase in igfbp5 expression, however, combination of flutamide+AI treatments caused increased protein expression. Expression of few of the molecules in PI3K/Akt kinase pathway in different treatments was determined.ConclusionsThe results suggest a role for E2 in the regulation of luteal steroidogenesis, morphology and proliferation. igfbp5 was identified as one the E2 responsive genes with important role in the mediation of E2 actions such as E2-induced phosphorylation of PI3K/Akt kinase pathway.Electronic supplementary materialThe online version of this article (doi:10.1186/s12958-016-0153-1) contains supplementary material, which is available to authorized users.

Hypothyroidism Reduces the Size of Ovarian Follicles and Promotes Hypertrophy of Periovarian Fat with Infiltration of Macrophages in Adult Rabbits

“…Our present results therefore suggest that the low expression of aromatase in the ovary could be related to the small size of large tertiary follicles (antral follicles). Likewise, this low aromatase expression in antral follicles of hypothyroid animals could be related to modifications in the formation and function of the corpus luteum [30], rather than changes in the folliculogenesis [31]. In this regard, hypothyroidism affects the proliferation, angiogenesis, and apoptosis in the corpus luteum of rats [32].…”

Luteal expression of factors involved in the metabolism and sensitivity to oestrogens in the dog during pregnancy and in non‐pregnant cycle

“…Interestingly, effects of oestrogens in the CL appear to vary among different species, depending on their concentration and local availability. Thus, for example, in the rat and rabbit, oestrogens have luteotropic potential, whereas exogenous administration of oestrogens in rhesus monkeys shortens luteal life span (Hassani et al., 1978 ; Karsc & Sutton, 1976 ; Miller & Keyes, 1978 ; Townson et al., 1996 ; Tripathy et al., 2016 ). In the guinea pig, E2 effects appear to be time‐dependent, as administration of oestrogens in early dioestrus induces uterus‐mediated luteolysis, while application after day 9 of dioestrus prolongs luteal function (Illingworth & Perry, 1973 ).…”

Characterization of sexual size dimorphism in mandarin fish and association with igfbp-5a/b regulation

“…The expression of igfbp-5a was signi cantly increased after overexpression of E2 in tongue sole, and PPI analyses showed that igfbp-5a was associated with dimorphism-related gene such as pappalysin-1 (X. H. . Tripathy (Tripathy et al, 2016) proposed that igfbp-5 may be one of the response genes to E2, and that inhibiting E2 content resulted in increased levels of igfbp-5 and reduced activation of igf1r, which led to reduced activation of PI3K and pAkt/PKB levels and inhibited growth.…”