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Helen Mason

Publications and source records attributed to Helen Mason.

8 recordsLinked to original sources
PubMed2006

Stage-specific expression of androgen receptor, follicle-stimulating hormone receptor, and anti-Müllerian hormone type II receptor in single, isolated, human preantral follicles: relevance to polycystic ovaries.

CONTEXT: Recent evidence indicates that the increase in follicle numbers seen in polycystic ovary syndrome occurs early in folliculogenesis, with androgens being a likely causative candidate. In primates and sheep, androgen excess in utero results in ovarian changes similar to those in polycystic ovary syndrome. There is also increasing interest in the role of anti-Müllerian hormone (AMH) in early folliculogenesis because AMH knockout mice have an early depletion of their stock of primordial follicles. Initiation and early folliculogenesis may therefore be under negative control by AMH and positive control by androgens. OBJECTIVE: Because AMH signals exclusively through its type II receptor (AMHRII), the aim of this study was to determine and colocalize the stage-specific expression of AMHRII, androgen receptor (AR), and FSH receptor (FSHR) mRNA in individual, well-characterized preantral follicles. METHOD: Follicles were isolated from human ovarian cortex obtained from either oophorectomies or cortical biopsies at cesarean section. Expression of AR, FSHR, and AMHRII mRNA was determined using a nested RT-PCR protocol. RESULTS: AR mRNA was not detected in any primordial follicles but was from the transitional stage onward. The number of AR-positive follicles increased at each progressive growth stage. The expression of AR preceded that of FSHR, and only a small percentage of primary follicles expressed FSHR. AMHRII expression was rarely detected. CONCLUSIONS: This is the first study to identify the expression of AR in human transitional follicles. Results suggest a role for androgens in promoting early follicle growth and challenging the hypothesis that AMH exerts a direct, inhibitory effect on follicles at this stage.

Adult↗
PubMed2006

Granulosa cell production of anti-Müllerian hormone is increased in polycystic ovaries.

CONTEXT: There has been renewed interest in anti-Müllerian hormone (AMH) because of its role in the ovary. Data on its actions are sparse, but it appears to inhibit follicle growth. Interestingly, serum AMH is two to three times higher in women with polycystic ovary (PCO) syndrome than women with normal ovaries. OBJECTIVE: We examined the production of AMH by cells from a range of follicle sizes from normal ovaries and compared this with production by ovulatory and anovulatory (anov) PCOs. DESIGN: Granulosa cells (GCs) and theca and follicular fluid (ff) were isolated from intact follicles. Cells were cultured for 48 h +/- FSH or LH, and AMH was measured in ff and cell-conditioned media (CM). RESULTS: AMH levels in ff and GC-CM ranged from 42 to 2240 and 0.025 to 1.7 ng/ml, respectively, and were low or undetectable in ff and GC-CM from follicles greater than 9 mm, luteinized cells, and theca and stroma. The mean level of AMH was four times higher in GC-CM from ovulatory PCOs [mean (range) 1.56 (0.025-7)] and 75 times higher from anovPCO [21.4 (17.2-43 ng/ml)] than normal ovaries [0.37 (0.025-1.7)]. Neither LH nor FSH had an effect on AMH production by GCs from normal ovaries, but in cells from PCOs, FSH significantly decreased AMH, and in contrast, LH increased AMH. CONCLUSIONS: The reduction of AMH in follicles greater than 9 mm from normal ovaries appears to be an important requirement for the selection of the dominant follicle. AMH production per GC was 75 times higher in anovPCOs, compared with normal ovaries. This increase in AMH may contribute to failure of follicle growth and ovulation seen in polycystic ovary syndrome.

Adult↗
PubMed2003

Substituted pyrazolopyridopyridazines as orally bioavailable potent and selective PDE5 inhibitors: potential agents for treatment of erectile dysfunction.

Novel pyrazolopyridopyridazine derivatives have been prepared as potent and selective PDE5 inhibitors. Compound 6 has been identified as a more potent and selective PDE5 inhibitor than sildenafil (1). It is as efficacious as sildenafil in in vitro and in vivo PDE5 inhibition models, and it is orally bioavailable in rats and dogs. The superior isozyme selectivity of 6 is expected to exert less adverse effects in humans when used for erectile dysfunction treatment.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2003

Metformin has direct effects on human ovarian steroidogenesis.

OBJECTIVE: To investigate the possibility of direct effects of metformin on ovarian steroidogenesis. DESIGN: Cultured ovarian cells. SETTING: Academic research environment. PATIENT(S): Women undergoing bilateral salpingoophorectomy for benign gynecological disease. MAIN OUTCOME MEASURE(S): Estradiol and P were measured in granulosa cell (GC) conditioned medium and androstenedione (A) and P in theca conditioned medium. RESULT(S): The effect of addition of metformin alone to GCs was variable, but significant inhibition of both P and E2 was seen (range 0%-30%). Metformin dose-dependently inhibited gonadotrophin and insulin-stimulated P and E2 production (range 25%-50%). In theca, metformin inhibited A production (0%-40%) with no effect on P. In the presence of insulin, A was inhibited dose-dependently and P increased by a similar magnitude. CONCLUSION(S): These results demonstrate a direct effect of metformin on ovarian steroidogenesis. The inhibitory effects on androgen production in particular would be beneficial in polycystic ovary syndrome (PCOS).

Adult↗
PubMed2002

Restoration of ovarian and uterine maturity in adolescents with anorexia nervosa.

OBJECTIVE: To determine the optimal weight-to-height ratio to achieve maturity of the reproductive organs when visualized by pelvic ultrasound in adolescent girls with anorexia nervosa. To examine the distribution of weight-to-height ratios in the group of adolescents in whom pelvic maturity was attained. METHODS: Adolescent girls with anorexia nervosa received serial transabdominal pelvic ultrasound scans as they regained weight. A record of their weight-to-height ratio had been noted on each occasion. The scans were defined as mature or immature using strict criteria. RESULTS: There was a wide range of weight-to-height ratios in both the mature and immature groups of patients with a considerable overlap between the groups. However, 88% of the sample required a weight-to-height ratio of 100% (body mass index [BMI] 20) to achieve reproductive maturity. CONCLUSION: Previous target weights have been too low to ensure reproductive maturity. The resulting hypoestrogenic state increases the risk of future osteoporosis. Pelvic ultrasound is the safest and most reliable method for determining ovarian and uterine maturity in adolescent girls with anorexia nervosa.

Adolescent↗
PubMed2002

Luteal phase progesterone excretion in ovulatory women with polycystic ovaries.

BACKGROUND: Various studies have reported a prevalence of polycystic ovaries (PCO) of approximately 20% in the 'normal' population. Our aim was to investigate the frequency of ovulation and pattern of luteal phase progesterone secretion in a group of women with PCO who reported regular cycles and in whom ovulation had been established on the basis of previous investigations. METHODS: Subjects collected early morning urine samples for pregnanediol-3-glucuronide measurement from day 10 of the cycle to day 1 of their next menses. Results in three consecutive cycles from women with PCO (group 1, n = 10 and 29 for patients and cycles respectively) were compared with results from two groups with normal ovaries; with either infertility (group 2, n = 10 and 30) or proven fertility (group 3, n = 6 and 19). RESULTS: There were considerable variations in cycle length. The median (range) was group 1: 28 (23-47); group 2: 26 (21-36) and group 3: 27 (25-38) days with more short cycles in both infertile groups. There was more variation in pregnanediol:creatinine in the normal-ovary infertile and PCO groups than in the fertile controls. Levels were higher in the early luteal phase in the fertile normal group than in either infertile group, and the mid-luteal phase peak was lower in the infertile women with normal ovaries. In summary, there was greater variability in luteal phase pregnanediol:creatinine ratios in the PCO and infertile normal-ovary groups than in women with normal ovaries and proven fertility. CONCLUSION: Women with PCO did not have more variation in cycle length than fertile women with normal ovaries, but there were significantly lower levels of progesterone in the early luteal phase. This may contribute to the delay in conception in these patients.

Adult↗
PubMed2000

Function of the polycystic ovary.

The mechanism of the increase in the number of follicles in polycystic ovaries (PCO) is still not understood, but most data indicate that folliculogenesis is abnormal at all stages. This increase is probably due to prolonged follicle growth in both ovulatory (ov) and anovulatory PCO (anovPCO) rather than over-recruitment from the primordial stage. There appear to be fewer follicles in ovPCO than in anovPCO and this may be due to slow growth combined with arrested development in the anovPCO, preventing the normal process of atresia. This idea is supported by data indicating that the preponderance of structures in anovPCO are functional follicles rather than atretic cysts. In contrast, follicles in ovPCO are primarily atretic, analogous to the situation in the normal ovary. Closer analysis of the function of these follicles reveals an intrinsic defect in the theca cell layer in the expression of the genes encoding steroidogenic enzymes. Although androgen production is increased in all PCOs, the serum concentrations of androgen tended to be higher in anovulatory women indicating that there may be a link between the ovarian concentration and anovulation. Granulosa cells in small follicles from anovPCO behave in a similar fashion to those in preovulatory follicles from normal ovaries in terms of steroidogenic responses. This, in combination with the finding of LH-responsiveness in small follicles from anovPCO, has led to the suggestion that these follicles are prematurely luteinized. The recent finding that follistatin gene regulation may be abnormal in women with polycystic ovary syndrome (PCOS) provides a new insight into the possible defect in the function of these ovaries. Elucidation of the precise nature of the defect may provide the key to understanding the apparent contradiction of increased steroidogenesis in the presence of abnormal and arrested follicle growth.

Journal Article↗