Prolactin (PRL) is a 23-kDa hormone produced by the pituitary and extrapituitary sites. The main target of PRL is the breast, where it affects cellular growth, differentiation, and milk production. Recent evidence suggests that locally produced PRL plays a role in breast tumorigenesis. Our objective was to examine PRL synthesis/release in different tissues of the human breast and determine the effect of ovarian steroids. Breast tissue, obtained from women undergoing mastectomy or breast reduction, was separated into glandular (nonmalignant) and adipose explants and incubated for 10 d. Conditioned media were analyzed for PRL by a bioassay. PRL release from glandular explants decreased by 60% from d 1-3, followed by a 4-fold increase on d 10. PRL release from adipose explants was unchanged from d 1-3 and increased more than 10-fold by d 10. PRL gene expression, determined by RT-PCR, was low on d 0 and markedly increased on d 10 in both types of explants. De novo synthesis of PRL was confirmed by metabolic labeling. Progesterone suppressed PRL release from glandular explants without affecting adipose explants. Estradiol did not alter PRL release from either tissue. In conclusion, the human breast produces and releases bioactive PRL, with a higher release rate by adipose than glandular tissue. The time-dependent rise in PRL release suggests removal from inhibitory control. Progesterone may be one of the factors that suppresses PRL production in the glandular compartment, whereas the factor(s) that regulate adipose PRL are unknown. These data suggest an autocrine/paracrine role for PRL in human glandular and adipose breast tissue.
Vaginal sildenafil citrate (Viagra, Pfizer, Inc., New York, NY) has been shown to be useful in increasing endometrial thickness and achieving pregnancy in women with varied uterine disorders. However, it failed to demonstrate favorable results in the setting of Asherman's syndrome, a condition characterized by the presence of uterine synechiae. We have successfully applied this treatment in two women noted to have inadequate endometrium after surgical resection of uterine synechiae. Both patients had a history of a postpartum uterine curettage with subsequent secondary infertility. Asherman's syndrome was surgically demonstrated and treated in both patients. Postoperatively, both patients were noted to have a thin endometrium and failed to conceive despite fertility treatment. Subsequently, these women achieved pregnancy in the first treatment cycle with vaginal sildenafil citrate. Using transvaginal ultrasound, endometrial thickness was noted to improve when sildenafil citrate was administered. It is suspected that this medication causes selective vasodilatation, resulting in improved endometrial development.
Abnormal strict morphologic assessment is both sensitive and specific for pregnancy outcomes in couples undergoing COH/IUI. Couples with persistently unfavorable sperm morphology should be counseled appropriately and would be better served by more aggressive treatment with in vitro fertilization and embryo transfer.
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