Polymorphisms in oestrogen and progesterone receptor genes: possible influence on prolactin levels in women.

OBJECTIVE: Oestrogen and progesterone are known to influence the release of human prolactin. The present study was undertaken in order to investigate the possible influence of polymorphisms of the genes encoding the oestrogen receptor (ER)alpha, ERbeta and the progesterone receptor (PGR), on prolactin levels in premenopausal women. DESIGN AND MEASUREMENTS: Serum levels of prolactin were measured in the follicular phase of the menstrual cycle. Subjects were genotyped with respect to a TA repeat polymorphism of the ERalpha gene, a CA repeat polymorphism of the ERbeta gene, and two polymorphisms of the PGR gene: one insertion polymorphism (PROGINS) and one single nucleotide polymorphism (G331A). SUBJECTS: A population-based cohort of 270 42-year-old women. RESULTS: The CA repeat polymorphism of the ERbeta gene and the G331A polymorphism of the PGR gene appeared to be associated with prolactin levels. In contrast, we found no evidence for an influence of the PROGINS polymorphism of the PGR gene or the TA repeat polymorphism of the ERalpha gene on the levels of this hormone. CONCLUSIONS: These data suggest that genetic variants of both the ERbeta and the PGR may influence prolactin release.

Diagnosis and treatment of premenstrual dysphoria.

Premenstrual dysphoria (PMD) is a severe form of premenstrual syndrome afflicting 5% to 10% of all fertile women. Cardinal symptoms--appearing regularly between ovulation and menstruation and disappearing within a few days after the onset of the bleeding--are depressed mood, tension, affect lability, and irritability. Of these symptoms, irritability is often the most prominent. Serotonin reuptake inhibitors (SRIs), but not nonserotonergic antidepressants, reduce the symptoms of PMD effectively. The onset of action of SRIs is much shorter when used for PMD than when used for depression, enabling women with PMD to restrict medication use to the luteal phase of the cycle (so-called intermittent treatment). The findings that SRIs are effective for PMD--and that sexual dysfunction is the most frequent side effect during long-term treatment--both lend support for the hypothesis that a major role for brain serotonin is to modulate sex steroid-driven behavior.

Postnatal endotoxin exposure results in increased insulin sensitivity and altered activity of neuroendocrine axes in adult female rats.

OBJECTIVES: Severe postnatal infection leads to a systemic inflammatory response with release of cytokines and glucocorticoids, representing a stressful event for the newborn child. The purpose of this study was to mimic this situation and to study the effects of early postnatal endotoxin exposure of female rat pups on metabolic, endocrine and anthropometric variables in adulthood. DESIGN: Female pups were given subcutaneous injections of lipopolysaccharides (LPS; Salmonella enteriditis, 0.05 mg/kg) or vehicle 3 and 5 days after birth. RESULTS: Six hours after injection, LPS-treated rats had higher corticosterone levels than controls. As adults, LPS-exposed female rats showed increased insulin sensitivity (P<0.05), measured with the hyperinsulinemic euglycemic clamp (5 mU/kg per min). They exhibited a higher locomotor activity (P<0.05) and increased skeletal muscle mass in comparison with controls (P<0.05). Basal ACTH and corticosterone levels in LPS-treated rats were elevated (P<0.05), as were corticosterone levels after exposure to a novel environment stress (P<0.05). The adrenals were morphologically changed and enlarged (P<0.05) in LPS-exposed rats at 11 weeks of age, and a higher density of hypothalamic but not hippocampal glucocorticoid receptor protein was found in the LPS-treated rats (P<0.05). Furthermore, circulating progesterone levels were lower (P<0.05) and testosterone tended to be higher. CONCLUSION: The results indicate that postnatal exposure to LPS leads to increased insulin sensitivity in the adult female rat. In addition, LPS-treated rats showed changes in the regulation of hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes. This study suggests that postnatal exposure to an endotoxin such as LPS can induce specific programming of neuroendocrine regulation, with long-term consequences in adult life.