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Pathogen research abs 1 || Pathogen research abs 2 || Pathogen research abs 3 || Pathogen research abs 4 || Pathogen research abs 5 || Hormone and endocrine research abs 1 || Hormone and endocrine research abs 2 || Hormone and endocrine research abs 3 || Hormone and endocrine research abs 4 || Hormone and endocrine research abs 5 || Follicle and follicular cells research abs 1

Endocrinology. 2003 Jan;144(1):154-62.
Lysyl oxidase gene expression and enzyme activity in the rat ovary: regulation by follicle-stimulating hormone, androgen, and transforming growth factor-beta superfamily members in vitro.

Harlow CR, Rae M, Davidson L, Trackman PC, Hillier SG.

University of Edinburgh, Department of Reproductive and Developmental Sciences, Edinburgh, Scotland EH16 4SB, United Kingdom. c.harlod.ac.uk

Lysyl oxidase (LOX) catalyzes the final enzymatic reaction required for cross-linking of collagen and elastin fibers and therefore has a crucial role in regulating the formation and maintenance of extracellular matrix in the ovary. LOX mRNA is abundantly expressed in rat granulosa cells. To examine how regulation of LOX in the ovary might influence follicular development, we studied LOX mRNA expression and enzyme activity in rat granulosa cells from late preantral/early antral follicles in vitro. FSH dose dependently inhibited LOX mRNA and enzyme activity (50% reduction at 10 ng/ml) in vitro, and FSH action was mimicked by 8-bromo-cAMP, suggesting FSH action via elevation of cAMP. Dihydrotestosterone alone enhanced LOX mRNA and enzyme activity, but potentiated the effect of FSH, causing a further reduction. TGFbeta1 alone dose dependently enhanced LOX mRNA (5-fold increase at 10 ng/ml) and activity (1.5-fold increase). FSH dose dependently inhibited the increase in LOX mRNA and activity caused by TGFbeta1 (by up to 84% and 80%, respectively). Growth differentiation factor-9 (GDF-9) and activin A, at the same concentration as TGFbeta1 (10 ng/ml), stimulated LOX mRNA and activity within 6 h, although overall expression was higher at 48 h. All three factors when combined with FSH further reduced both mRNA and enzyme activity (by up to 60%) compared with FSH alone. These findings indicate control of LOX at endocrine, paracrine, and autocrine levels within the ovary and suggest coordinated regulation of ovarian extracellular matrix during follicular development, with FSH determining whether local factors act as stimulators or inhibitors of LOX.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12488341&dopt=Abstract

Hum Reprod. 2002 Aug;17(8):1987-93.
Single dose pharmacokinetics and effects on follicular growth and serum hormones of a long-acting recombinant FSH preparation (FSH-CTP) in healthy pituitary-suppressed females.

Duijkers IJ, Klipping C, Boerrigter PJ, Machielsen CS, De Bie JJ, Voortman G.

Dinox Medical Investigations, Groenewoudseweg 317, 6524 TX, Nijmegen, The Netherlands. dinoolyvos.net

BACKGROUND: A long-acting FSH preparation has been developed by site-directed mutagenesis and gene transfer techniques. METHODS: In this open-label trial, we investigated the pharmacokinetic and pharmacodynamic properties of FSH-CTP (corifollitropin alpha, Org 36286) in healthy female volunteers. Twenty-four subjects were treated with a high-dose oral contraceptive (OC) to suppress pituitary function. A single dose of 15, 30 or 60 micro g FSH-CTP was injected (s.c., eight subjects per dose group) and seven of these 24 subjects were subsequently treated with a single dose of 120 micro g. RESULTS: Maximum serum FSH-CTP concentrations (0.42, 0.66, 1.49 and 3.27 ng/ml after administration of 15, 30, 60 and 120 micro g Org 36286 respectively) were reached between 36 and 48 h after injection and t(1/2) varied between 60 and 75 h. Dose proportionality was shown across the studied dose range, whereas t(max) and t(1/2) were dose independent. In most subjects follicular growth was observed; the number and maximum diameter of the follicles increased with the dose. Follicles with a diameter vertical line 8.0 mm were observed only in the 60 and 120 micro g dose groups, diameters between 12.0 and 15.9 mm occurred only in the 120 micro g group. Serum LH and 17beta-oestradiol levels remained low due to profound pituitary suppression whereas inhibin-B levels increased with dose. Maximum mean inhibin-B levels were 30.4, 322.7 and 1059.3 pg/ml in the 30, 60 and 120 micro g dose group respectively. The preparation was safe and well tolerated, and no FSH-CTP antibody formation was observed. CONCLUSIONS: The pharmacokinetics of FSH-CTP were shown to be proportional with the dose. The elimination half-life was approximately two times longer than that of rFSH. A single dose of FSH-CTP was shown to be safe and able to induce multiple follicular growth accompanied by a dose-dependent rise in serum inhibin-B concentrations.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12151425&dopt=Abstract

Hum Reprod. 2002 Aug;17(8):2079-84.
Phosphodiesterase 3 inhibitors selectively block the spontaneous resumption of meiosis by macaque oocytes in vitro.

Jensen JT, Schwinof KM, Zelinski-Wooten MB, Conti M, DePaolo LV, Stouffer RL.

Department of Obstetrics and Gynecology and Division of Reproductive Sciences, Oregon Regional Primate Research Center, Oregon Health & Science University, Portland, OR 97201, USA. jensenjhsu.edu

BACKGROUND: The purpose of this study was to determine whether phosphodiesterase (PDE) 3 inhibitors selectively prevent the resumption of meiosis in primates. METHODS: Immature oocytes (intact germinal vesicles) obtained from large pre-ovulatory follicles following ovarian stimulation in rhesus macaques were incubated with or without various doses of the PDE3 inhibitors, Cilostamide, Milrinone or ORG 9935, or a selective PDE4 inhibitor, Rolipram. Oocytes were observed for germinal vesicle breakdown (GVBD) as an indicator of resumption of meiosis. RESULTS: At 24 h, 72 of 121 (60%) control oocytes progressed to GVBD compared with 9/34 (27%, P < 0.01), 4/36 (11.1%, P < 0.01) and 0/28 (0%, P < 0.01) oocytes incubated with ORG 9935 at 0.1, 0.5 and 1.0 micromol/l respectively. Similar results were achieved at 24 h with 1.0 micromol/l Cilostamide (2/24 oocytes, 8%, P < 0.01) and 100 micromol/l Milrinone (2/32, 6%, P < 0.01). In contrast, no significant difference in GVBD was noted between control oocytes and those incubated with up to 100 micromol/l Rolipram for 24 h (43/58, 74%) or 48 h (44/58, 76%). CONCLUSIONS: These experiments establish the specificity and dose-dependent ability of PDE3, but not PDE4, inhibitors to block resumption of meiosis in macaque oocytes in vitro. Thus, PDE3 inhibitors have potential use as contraceptives in primates.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12151440&dopt=Abstract

Hum Reprod. 2002 Aug;17(8):2152-9.
Effect of preantral follicle isolation technique on in-vitro follicular growth, oocyte maturation and embryo development in mice.

Demeestere I, Delbaere A, Gervy C, Van Den Bergh M, Devreker F, Englert Y.

Research Laboratory on Human Reproduction, Erasme Hospital, French Speaking Free University of Brussels, Route de Lennik 808, 1070 Brussels, Belgium. idemeeslb.ac.be

BACKGROUND: The use of mechanical and enzymatic techniques to isolate preantral follicles before in-vitro culture has been previously described. The aim of this study was to assess the effect of the isolation procedure of mouse preantral follicles on their subsequent development in vitro. METHODS: Follicles were isolated either mechanically or enzymatically and cultured using an individual non-spherical culture system. Follicular development and steroidogenesis, oocyte in-vitro maturation and embryo development were assessed for both groups. RESULTS: After 12 days of culture, follicles isolated mechanically had a higher survival rate but a lower antral-like cavity formation rate than follicles isolated enzymatically. Enzymatic follicle isolation was associated with a higher production of testosterone and estradiol compared with mechanical isolation. A stronger phosphatase alkaline reaction was observed after enzymatic isolation, suggesting that follicles isolated enzymatically had more theca cells than those isolated mechanically. However, both isolation techniques resulted in similar oocyte maturation and embryo development rates. CONCLUSIONS: Enzymatic follicular isolation did not affect theca cell development. Follicular steroidogenesis was enhanced after enzymatic isolation but the developmental capacity of oocytes was comparable to that obtained after mechanical isolation.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12151451&dopt=Abstract

Toxicol Sci. 2002 Aug;68(2):473-8.
Methoxychlor may cause ovarian follicular atresia and proliferation of the ovarian epithelium in the mouse.

Borgeest C, Symonds D, Mayer LP, Hoyer PB, Flaws JA.

Program in Toxicology, University of Maryland, Baltimore, Maryland 21201, USA.

Methoxychlor (MXC) is currently used to protect agricultural products from insects. Previous studies show that MXC adversely affects the ovary, but the target cells were not revealed by those studies. Therefore, the purpose of this study was to test the hypothesis that MXC induces ovarian changes by adversely affecting the antral follicles and the ovarian surface epithelium in the mouse. To test this hypothesis, cycling female CD-1 mice (39 days) were dosed with MXC (8, 16, or 32 mg/kg/day), kepone (KPN, 8 mg/kg/day, positive control), or sesame oil (vehicle control) via intraperitoneal injection for 10 or 20 days. Estrous cyclicity was evaluated daily via vaginal lavage. After dosing, ovaries were collected for histological evaluation of follicle numbers, atresia, and surface epithelial height. The results indicate that at the 20-day time point, MXC (32 mg/kg) and KPN (8 mg/kg) increased the percentage of atretic antral follicles (n= 4-9,p<or= 0.001). MXC (32 mg/kg) also increased the height of the ovarian surface epithelium compared with controls (n= 7-10,p<or= 0.045), and KPN increased the percentage of days in estrus (n= 6-10,p<or= 0.0001). These data suggest that MXC and KPN increase antral follicle atresia, MXC increases surface epithelial height, and KPN affects vaginal cytology.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12151644&dopt=Abstract

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