The Microenvironment of the Human Antral Follicle: Interrelationships among the Steroid Levels in Antral Fluid, the Population of Granulosa Cells, and the Status of the Oocyte in Vivo and in Vitro *

McNatty, Kenneth P.; Smith, Deborah Deutsch; Makris, Anastasia; Osathanondh, R; Ryan, Kenneth J.

doi:10.1210/jcem-49-6-851

Cited by 505 publications

(154 citation statements)

References 28 publications

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“…The granulosa cells from the 9 mm follicle showed less aromatase activity than those from the smaller follicles, the most likely explanation being that the 9 mm follicle was atretic. This was supported by the fact that only 280 000 granulosa cells were derived from this follicle compared with the expected number of more than 2 000 000 in a healthy follicle of this size (McNatty et al 1979). The conversion of DHEAS to oestradiol by the granulosa cells from the 7 mm follicle was 20%, in comparison to approximately 12% by the luteinized granulosa cells.…”

Section: Discussionmentioning

confidence: 65%

Human granulosa cells are a site of sulphatase activity and are able to utilize dehydroepiandrosterone sulphate as a precursor for oestradiol production

Bonser¹,

Walker²,

Purohit³

et al. 2000

Journal of Endocrinology

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Dehydroepiandrosterone sulphate (DHEAS) is the most abundant androgen in the circulation and in ovarian follicular fluid. A steroid sulphatase accepting DHEAS as a substrate has been identified in the follicle, but the cellular location has not been determined. As DHEAS is also a potential source of oestrogen for endocrine-dependent tumours, a potent steroid sulphatase inhibitor oestrone-3-O-sulphamate (EMATE) has been developed which inhibits this activity in rat liver and mammary tumour. The aim of this study was to investigate human granulosa cells as a site of steroid sulphatase activity, to determine whether DHEAS can be utilized as a precursor for oestrogen synthesis and to investigate the inhibitory capacity of EMATE in these cells. Conversion of DHEAS to DHEA was assessed in luteinized granulosa cells by tritiated steroid assay following incubation with or without LH or insulin and steroid accumulation in the medium measured by RIA. The effects of EMATE were assessed by addition of a range of doses during the measurement of conversion of DHEAS to DHEA. Cells from three sizes of small follicles from an unstimulated ovary were also assessed for their ability to produce oestradiol from DHEAS.Sulphatase enzyme activity was present in all cells; the mean conversion of tritiated DHEAS to DHEA was 50% (range 4-65%). LH and EMATE inhibited and insulin stimulated this activity. Addition of DHEAS to granulosa cells caused a dose-dependent increase in oestradiol and androstenedione production with no change in progesterone concentration. LH increased the accumulation of oestradiol in the medium. DHEAS also stimulated oestradiol production by granulosa cells from small follicles. This is the first demonstration that granulosa cells are a site of sulphatase activity and that DHEAS can be utilized as a substrate for androstenedione and oestrogen production. This may be of physiological importance for both normal folliculogenesis and oestrogen-dependent tumour growth.

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Section: Discussionmentioning

confidence: 65%

Human granulosa cells are a site of sulphatase activity and are able to utilize dehydroepiandrosterone sulphate as a precursor for oestradiol production

Bonser¹,

Walker²,

Purohit³

et al. 2000

Journal of Endocrinology

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“…In normal ovulatory cycles, a higher concentration of E2 in follicular fluid (FF) is associated with healthy follicles that contain oocytes capable of meiosis, and higher concentrations of androgens indicative of atretic changes (degeneration and subsequent resorption of the follicles) (Greenwald & Roy, 1994;Speroff, Glass, & Kase, 1999). The majority of earlier studies of steroids in ovarian follicles (McNatty et al, 1979;Dehennin, Jondet, & Scholler, 1987a,b;Itskovitz et al, 1991) were undertaken to obtain prognostic parameters for the likelihood of a successful implantation during in vitro fertilization (IVF); however, the relationship between steroid hormones and follicular development in regularly menstruating (RM) healthy women was not well studied. In part, this is related to the very small sample size of FF that could be obtained from follicles of healthy women during the follicular stage of menstrual cycle, and absence of sensitive and specific methods for simultaneous quantitation of multiple steroids in small samples.…”

Section: Steroids In Ovarian Follicles Of Healthy Womenmentioning

confidence: 99%

Liquid chromatography-tandem mass spectrometry applications in endocrinology

Kushnir

Rockwood

Bergquist

2009

Mass Spectrom. Rev.

138

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Liquid chromatography-tandem mass spectrometry (LC-MS/ MS) has been recognized as a primary methodology for the accurate analysis of endogenous steroid hormones in biological samples. This review focuses on the use of LC-MS/MS in clinical laboratories to assist with the diagnosis of diverse groups of endocrine and metabolic diseases. Described analytical methods use on-line and off-line sample preparation and analytical derivatization to enhance analytical sensitivity, specificity, and clinical utility. Advantages of LC-MS/MS as an analytical technique include high specificity, possibility to simultaneously measure multiple analytes, and the ability to assess the specificity of the analysis in every sample. All described analytical methods were extensively validated, utilized in routine diagnostic practice, and were applied in a number of clinical and epidemiological studies, including a study of the steroidogenesis in ovarian follicles. #

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“…For example, in ovaries of women aged 25-49 years, 2 antral follicles (4 mm diameter) from the population of all antral follicles (ie 14-50%) contain a full complement of viable GC. 27,28 After exogenous gonadotropin treatments to enhance oocyte yields in sheep or humans, measures of GC functions (ie cAMP synthesis in vitro) or gene expression profiles of CC from oocytes before IVF, suggest that the hierarchical pattern of follicular development is not overcome. 4,14 This suggests that most of these exogenously-treated follicles that yield oocytes were probably rescued from atresia.…”

Section: Introductionmentioning

confidence: 99%

Oocyte-Somatic Cell Interactions and Ovulation Rate: Effects on Oocyte Quality and Embryo Yield

McNatty¹,

Juengel²,

Pitman³

2014

Reproductive Biology Insights

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ABSTRACT:The use of exogenous gonadotropins to increase oocyte yields for better pregnancy outcomes remains unpredictable and inefficient. The objectives of this review are to address two questions concerning this issue: (1) are there any alternatives for improving consistency in oocyte yields? (2) is it possible to develop a molecular diagnostic test for oocytes with blastocyst potential? Studies in sheep with a heterozygous inactivating mutation in the oocyte-derived growth factor, bone morphogenetic protein 15 (BMP15), report increased oocyte yields and significantly more offspring. Moreover, partial immuno-neutralization of BMP15 bioactivity increases oocyte yield without modifying gonadotropin or ovarian steroid secretion. Therefore, it is hypothesized that the development of BMP15 antagonists may prove them to be suitable alternatives to exogenous gonadotropins. Recent evidence from analyses of candidate gene expression in human cumulus cells separated from individual oocytes before IVF indicates a potential non-invasive molecular screen for oocytes with improved blastocyst and live-birth outcomes.

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The Microenvironment of the Human Antral Follicle: Interrelationships among the Steroid Levels in Antral Fluid, the Population of Granulosa Cells, and the Status of the Oocyte in Vivo and in Vitro *

Cited by 505 publications

References 28 publications

Human granulosa cells are a site of sulphatase activity and are able to utilize dehydroepiandrosterone sulphate as a precursor for oestradiol production

Human granulosa cells are a site of sulphatase activity and are able to utilize dehydroepiandrosterone sulphate as a precursor for oestradiol production

Liquid chromatography-tandem mass spectrometry applications in endocrinology

Oocyte-Somatic Cell Interactions and Ovulation Rate: Effects on Oocyte Quality and Embryo Yield

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