Influence of High-Density Lipoprotein on Estradiol Stimulation of Luteal Steroidogenesis
1

Khan, Iqbal; Bélanger, Alain; Chen, Y D; Gibori, Geula

doi:10.1095/biolreprod32.1.96

Cited by 31 publications

(5 citation statements)

References 29 publications

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“…Thus, the increase in ERβ may have increased the ovarian response to circulating E 2 , which in turn stimulates cyp19A1 aromatase expression and E 2 synthesis. These data suggest that the negative feedback exerted by E 2 may be partially blocked in HypoT rats, sensitizing the ovary to E 2 actions during P and E. Since it has been largely demonstrated that, in the rat, E 2 stimulates steroidogenesis and luteal hypertrophy and synergizes with the effect of PRL in the ovary, these factors may promote corpus luteum survival favouring the establishment of pseudopregnancy [26,34-37]. …”

Section: Discussionmentioning

confidence: 99%

Short term hypothyroidism affects ovarian function in the cycling rat

Hapon

Gamarra-Luques

Jahn³

2010

Reprod Biol Endocrinol

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BackgroundRats made hypothyroid with propilthyouracil start showing abnormal cycling on the second cycle after the start of the treatment, with a high proportion of spontaneous pseudopregnancies and reduced fertility.MethodsTo investigate some of the mechanisms involved in these reproductive abnormalities, hypothyroidism was induced in virgin rats by propilthyouracil (0.1 g/L in the drinking water) and we determined circulating hormones by radioimmunoassay and whole ovary expression of ovarian hormone receptors, growth factors and steroidogenic enzymes using semi-quantitative RT-PCR.The study was performed on days 6 to 9 of treatment, corresponding to diestrus I (at 20.00-22.00 h), diestrus II (at 20.00-22.00 h), proestrus and estrus (both at 8.00-10.00 h and 20.00-22.00 h) of the second estrous cycle after beginning propilthyouracil treatment. Another group of rats was mated on day 8 and the treatment continued through the entire pregnancy to evaluate reproductive performance.ResultsHypothyroidism increased circulating prolactin and estradiol on estrus 5 to 7-fold and 1.2 to 1.4-fold respectively. Growth hormone and insulin-like growth factor 1 diminished 60 and 20% respectively on proestrus morning. Hypothyroidism doubled the ovarian mRNA contents of estrogen receptor-beta on proestrus and estrus evenings, cyp19A1 aromatase mRNA on estrus evening and of growth hormone receptor on proestrus evening. Hypothyroidism did not influence ovulation rate or the number of corpora lutea at term, but a diminished number of implantation sites and pups per litter were observed (Hypothyroid: 11.7 +/- 0.8 vs. Control: 13.9 +/- 0.7).ConclusionsShort term hypothyroidism alters normal hormone profile in the cycling rat increasing the expression of estrogen receptor-beta and cyp19A1 aromatase on estrus, which in turn may stimulate estradiol and prolactin secretion, favouring corpus luteum survival and the subsequent instauration of pseudopregnancy.

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Section: Discussionmentioning

confidence: 99%

Short term hypothyroidism affects ovarian function in the cycling rat

Hapon

Gamarra-Luques

Jahn³

2010

Reprod Biol Endocrinol

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“…Since the rat ovary appears to utilize high density lipoproteins (HDL) as a preferred cholesterol source for steroid production [66], the diabetes-associated increase in very low density lipoprotein that coincides with the marked decline in hepatic HDL levels [20] may limit ovarian (CL) steroid production. Although the CL can synthesize cholesterol de novo [67], the magnitude of the lipoprotein imbalance in diabetes with the significant decrease in HDL-derived cholesterol may exceed the synthetic capacity of the ovary to generate endogenous cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Altered Ovarian Sterol Carrier Protein Expression in the Pregnant Streptozotocin-Treated Diabetic Rat1

McLean

Warden

Sandhoff

et al. 1996

Biology of Reproduction

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Reproductive dysfunction in the diabetic female rat is associated with impaired folliculogenesis, reduced corpus luteum progesterone output, and spontaneous abortion. The underlying mechanism for reduced steroid production remains unresolved. In this study we examined whether or not diabetes alters levels of P450 side-chain cleavage enzyme (P450scc), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD), or the cholesterol transport proteins, steroidogenic acute regulatory (StAR) protein and sterol carrier protein-2 (SCP2), leading to lower progesterone levels and pregnancy loss. Rats (Day 3 pregnant) received an injection of streptozotocin (STZ, 60 mg/kg; i.v.) to induce a diabetic state; P450scc, 3 beta-HSD, and SCP2 were examined by Western and Northern blot analysis in ovarian tissue 12 days after injection of STZ (diabetic rats, n = 12) or vehicle (nondiabetic rats, n = 12). Serum progesterone, triglyceride, and beta-hydroxybutyrate (beta-HBA) levels were also examined. Results indicate that diabetic rats that aborted (diabetic-fetus [Ft], n = 6) had significantly lower progesterone levels (7.04 +/- 2.6 ng/ml; p < 0.004) than nondiabetic animals (108.6 +/- 5.15 ng/ml) and diabetic +Ft animals (74.3 +/- 8.9 ng/ml, n = 6). Western blot analysis of ovarian P450scc and 3 beta-HSD in the nondiabetic rats and the diabetic rats with fetuses indicated no significant difference. In contrast, ovaries from diabetic animals without fetuses had significantly lower SCP2 levels (p < 0.017) compared to controls. Concomitant with the reduction in SCP2, a 58-kDa SCP2-immunoreactive protein, referred to as sterol carrier protein-X (SCPx), increased significantly (p < 0.001). The C-terminal sequence of SCPx is identical to SCP2, while its N-terminal region is homologous with 3-oxoacyl coenzyme A thiolase, an enzyme involved in fatty acid metabolism. Increased SCPx expression coincided with increased serum triglyceride and beta-HBA levels, suggesting that the enhanced SCPx level may coincide with an ovarian shift to fatty acid metabolism. When SCPx steady-state mRNA levels were measured using an SCPx-specific riboprobe (280-bp protected fragment) in a ribonuclease protection assay, ovarian SCPx mRNA levels in the diabetic animals were increased 4.2-fold compared to control SCPx mRNA levels. Ovarian StAR mRNA levels were increased slightly in the diabetic animals, and ovarian P450scc and 3 beta-HSD mRNA levels were increased 3-fold in the diabetic animals that aborted relative to the nondiabetic animals and the +Ft diabetic animals. Results of this study confirm that SCPx mRNA levels are elevated following diabetes onset and that StAR, P450scc, and 3 beta-HSD mRNA levels do not correspond with the reduced steroid hormone profile associated with diabetes. These results are concordant with the possibility that reduced steroid levels in the diabetic animals reflect a loss of SCP2-mediated cholesterol transport capacity as SCPx/3-oxoacyl coenzyme A thiolase expression is enhanced.

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“…We originally thought that the involvement of HSD17B7 in cholesterol biosynthesis in the corpus luteum is of little importance because the cholesterol used by the ovary originates from circulating lipoprotein (34,35). However, the marked expression of this enzyme in the fetal brain and the fact the viability of neurons depends on the intracellular cholesterol content and not on the intermediate nonsterol isoprenoid products (30) made us reconsider the importance of this activity in brain formation.…”

Section: Fig 6 Expression Of Hsd17b7 In the Embryo By In Situ Hybrimentioning

confidence: 99%

Prolactin Receptor-Associated Protein/17β-Hydroxysteroid Dehydrogenase Type 7 Gene (Hsd17b7) Plays a Crucial Role in Embryonic Development and Fetal Survival

Shehu¹,

Mao²,

Gibori³

et al. 2008

Molecular Endocrinology

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Our laboratory has previously cloned and purified a protein named PRAP (prolactin receptor-associated protein) that was shown to be a novel 17beta-hydroxysteroid dehydrogenase (HSD) enzyme with dual activity. This enzyme, renamed HSD17B7 or PRAP/17beta-HSD7, converts estrone to estradiol and is also involved in cholesterol biosynthesis. The major site of its expression is the corpus luteum of a great number of species including rodents and humans. To examine the functional significance of HSD17B7 in pregnancy, we generated a knockout mouse model with targeted deletions of exons 1-4 of this gene. We anticipated a mouse with a severe fertility defect due to its inability to regulate estrogen levels during pregnancy. The heterozygous mutant mice are normal in their development and gross anatomy. The females cycle normally, and both male and female are fertile with normal litter size. To our surprise, the breeding of heterozygous mice yielded no viable HSD17B7 null mice. However, we found HSD17B7 null embryo alive in utero on d 8.5 and d 9.5. By d 10.5, the fetuses grow and suffer from severe brain malformation and heart defect. Because the brain depends on in situ cholesterol biosynthesis for its development beginning at d 10, the major cause of fetal death appears to be due to the cholesterol synthetic activity of this enzyme. By ablating HSD17B7 function, we have uncovered, in vivo, an important requirement for this enzyme during fetal development.

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Influence of High-Density Lipoprotein on Estradiol Stimulation of Luteal Steroidogenesis 1

Cited by 31 publications

References 29 publications

Short term hypothyroidism affects ovarian function in the cycling rat

Short term hypothyroidism affects ovarian function in the cycling rat

Altered Ovarian Sterol Carrier Protein Expression in the Pregnant Streptozotocin-Treated Diabetic Rat1

Prolactin Receptor-Associated Protein/17β-Hydroxysteroid Dehydrogenase Type 7 Gene (Hsd17b7) Plays a Crucial Role in Embryonic Development and Fetal Survival

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