The role of progesterone in regulating human granulosa cell proliferation and differentiation in vitro.

Chaffkin, Linda M.; Luciano, Anthony A.; Peluso, John J.

doi:10.1210/jcem.76.3.8445028

Cited by 27 publications

(13 citation statements)

References 22 publications

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“…In further confirmation of an autocrine signaling mechanism, we demonstrate that inhibition of the synthesis of progesterone with AMG, a p450scc inhibitor, prevents NRC proliferation. A number of studies have shown that progesterone has previously been shown to regulate proliferation and protect cells from apoptosis in autocrine/paracrine mechanisms (15,47,55). Since cholangiocyte secretion of progesterone is downregulated by BDL, serum levels of progesterone (which are considerably elevated in serum compared with cholangiocyte supernatants) indicate that the paracrine signaling mechanism may play a role during cholestasis.…”

Section: Discussionmentioning

confidence: 99%

Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms

Glaser¹,

DeMorrow²,

Francis³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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During cholestatic liver diseases, cholangiocytes express neuroendocrine phenotypes and respond to a number of hormones and neuropeptides by paracrine and autocrine mechanisms. We examined whether the neuroendocrine hormone progesterone is produced by and targeted to cholangiocytes, thereby regulating biliary proliferation during cholestasis. Nuclear (PR-A and PR-B) and membrane (PRGMC1, PRGMC2, and mPRα) progesterone receptor expression was evaluated in liver sections and cholangiocytes from normal and bile duct ligation (BDL) rats, and NRC cells (normal rat cholangiocyte line). In vivo, normal rats were chronically treated with progesterone for 1 wk, or immediately after BDL, rats were treated with a neutralizing progesterone antibody for 1 wk. Cholangiocyte growth was measured by evaluating the number of bile ducts in liver sections. The expression of the progesterone synthesis pathway was evaluated in liver sections, cholangiocytes and NRC. Progesterone secretion was evaluated in supernatants from normal and BDL cholangiocytes and NRC. In vitro, NRC were stimulated with progesterone and cholangiocyte supernatants in the presence or absence of antiprogesterone antibody. Aminoglutethimide was used to block progesterone synthesis. Cholangiocytes and NRC express the PR-B nuclear receptor and PRGMC1, PRGMC2, and mPRα. In vivo, progesterone increased the number of bile ducts of normal rats, whereas antiprogesterone antibody inhibited cholangiocyte growth stimulated by BDL. Normal and BDL cholangiocytes expressed the biosynthetic pathway for and secrete progesterone. In vitro, 1) progesterone increased NRC proliferation; 2) cholangiocyte supernatants increased NRC proliferation, which was partially inhibited by preincubation with antiprogesterone; and 3) inhibition of progesterone steroidogenesis prevented NRC proliferation. In conclusion, progesterone may be an important autocrine/paracrine regulator of cholangiocyte proliferation.

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Section: Discussionmentioning

confidence: 99%

Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms

Glaser¹,

DeMorrow²,

Francis³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The LH surge not only induces ovulation but also stimulates GCs of the preovulatory follicle to luteinize which results in transformation of the follicle in the corpus luteum. It appears that LH surge acts as a "switch", preventing cell proliferation and initiating luteinization, as evidenced by enhanced progesterone synthesis (8). It should be stressed that GCs were harvested closely before ovulation from corona radiata and a part of cumulus oophorus of hormonally stimulated women.…”

Section: Discussionmentioning

confidence: 99%

The Cultivation of Human Granulosa Cells

Brůčková

Soukup

Moos

et al. 2008

Acta Med. (Hradec Kralove, Czech Repub.)

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Summary:The major functions of granulosa cells (GCs) include the production of steroids, as well as a myriad of growth factors to interact with the oocyte during its development within the ovarian follicle. Also FSH stimulates GCs to convert androgens (coming from the thecal cells) to estradiol by aromatase. However, after ovulation the GCs produce progesterone that may maintain a potential pregnancy. Experiments with human GCs are mainly focused on the purification of GCs from ovarian follicular fluid followed by FACS analysis or short-term cultivation. The aim of our study was to cultivate GCs for a long period, to characterize their morphology and phenotype. Moreover, we have cultivated GCs under gonadotropin stimulation in order to simulate different pathological mechanisms during folliculogenesis (e.g. ovarian hyperstimulation syndrome). GCs were harvested from women undergoing in vitro fertilization. Complex oocyte-cumulus oophorus was dissociated by hyaluronidase. The best condition for transport of GCs was optimized as short transport in follicular fluid at 37 °C. GCs expansion medium consisted of DMEM/F12, 2 % FCS, ascorbic acid, dexamethasone, L-glutamine, gentamycine, penicillin, streptomycin and growth factors (EGF, bFGF). GCs transported in follicular fluid and cultivated in 2 % FCS containing DMEM/F12 medium supplemented with follicular fluid presented increased adhesion, proliferation, viability and decreased doubling time. Cell viability was 92 % and mean cell doubling time was 52 hrs. We have optimized transport and cultivation protocols for long-term cultivation of GCs.

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“…This nonsurgical, reversible method of LH ablation and replacement will allow further studies examining the role of LH in the regulation of specific structural and functional properties of the primate corpus luteum. Studies supporting a role for progesterone in the regulation of luteal structure (8), pro-gesterone production (8,44), and LH receptor expression (9) could be advanced by using this model in conjunction with steroid synthesis inhibitors (8) to further elucidate the role of progesterone in the regulation of the structure and functional life span of the corpus luteum in an environment of sustained gonadotropin support.…”

Section: Discussionmentioning

confidence: 99%

Titrating Luteinizing Hormone Replacement to Sustain the Structure and Function of the Corpus Luteum after Gonadotropin-Releasing Hormone Antagonist Treatment in Rhesus Monkeys1

Duffy

Stewart

Stouffer

1999

The Journal of Clinical Endocrinology &Amp; Metabolism

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These studies were designed to identify 1) a regimen of a third generation GnRH antagonist that abolishes primate luteal function, and 2) the amount of LH replacement required to maintain the structure and functional life span of the corpus luteum of the menstrual cycle after GnRH antagonist treatment. A single injection of antide at 3 or 5 mg/kg BW on day 6 of the luteal phase suppressed serum progesterone levels within 1 day of treatment, but levels recovered within 4 days. Administration of antide (3 mg/kg) for 3 days (luteal days 6 -8) reduced (P Ͻ 0.05) serum progesterone below 1 ng/mL and maintained these low levels for the entire sampling period; in subsequent experiments, all monkeys received this antide regimen. Fixed doses (5, 10, or 20 IU) of recombinant human LH administered at 8-h intervals during and after antide treatment stimulated progesterone production in a dose-dependent manner; these monkeys menstruated earlier than controls regardless of treatment group. Replacement with an escalating dose regimen (5-20 IU) of LH resulted in typical serum progesterone and relaxin levels throughout a luteal phase of normal length. Corpora lutea removed on day 10 from monkeys treated with antide alone had decreased wet weight (P Ͻ 0.05) and few large luteal cells; coadministration of the escalating dose regimen of LH maintained luteal structure similar to that seen in time-matched controls. Antide-only treatment increased progesterone receptor (PR) messenger ribonucleic acid, but decreased PR immunostaining in luteal tissue; the escalating dose regimen of LH maintained PR messenger ribonucleic acid and immunostaining similar to those in controls. This study indicates that during GnRH antagonist administration, an escalating dose regimen of LH replacement is optimal for maintenance of the structure and functional life span of the primate corpus luteum. (J Clin Endocrinol Metab 84: 342-349, 1999) L H IS ESSENTIAL for the proper development and function of the primate corpus luteum during the menstrual cycle. Administration of antibodies against LH to monkeys caused a premature decline of progesterone production (1), demonstrating the dependence of luteal function on continued LH exposure. After ablation of endogenous gonadotropin release by administration of a GnRH antagonist, replacement of gonadotropin activity with LH, but not FSH, restored luteal function (2). Administration of hCG, a LH-like gonadotropin, was also able to stimulate luteal progesterone production (3). However, the amount and pattern of LH exposure required to maintain the normal structure and functional life span of the corpus luteum of the menstrual cycle are unknown.Studies have examined the roles of LH pulse amplitude and frequency in the maintenance of the primate corpus luteum. In the macaque, frequent LH pulses of lower amplitude were measured in serum early in the luteal phase, but by days 10 -11 of the luteal phase, higher amplitude LH pulses were measured only three times daily (4). Monkeys with radiofrequency lesions to...

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The role of progesterone in regulating human granulosa cell proliferation and differentiation in vitro.

Cited by 27 publications

References 22 publications

Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms

Progesterone stimulates the proliferation of female and male cholangiocytes via autocrine/paracrine mechanisms

The Cultivation of Human Granulosa Cells

Titrating Luteinizing Hormone Replacement to Sustain the Structure and Function of the Corpus Luteum after Gonadotropin-Releasing Hormone Antagonist Treatment in Rhesus Monkeys1

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