Anti-prolactin autoantibodies in pregnant women with systemic lupus erythematosus: maternal and fetal outcome.

The aim of this study was to determine in pregnant women with systemic lupus erythematosus (SLE) the frequency of anti-prolactin autoantibodies and to compare the outcome of pregnancy in SLE women with and without anti-prolactin autoantibodies. Ninety-nine consecutive SLE pregnant women and 151 healthy pregnant women were studied prospectively. Patients with or without anti-prolactin autoantibodies were identified by gel filtration chromatography and affinity chromatography for IgG. Serum total and free prolactin (PRL) levels and molecular heterogeneity of PRL at each trimester of pregnancy were determined. The frequency of anti-PRL autoantibodies in SLE pregnant women was 13.1%. Serum total PRL levels were significantly higher in women with anti-PRL autoantibodies compared with SLE women without anti-PRL autoantibodies and in healthy pregnant women; and serum free PRL levels were lower in the third trimester in women with anti-PRL autoantibodies than in healthy pregnant women. In contrast, serum total and free PRL levels were significantly lower in the second and third trimester in SLE pregnant women without anti-PRL autoantibodies compared with healthy pregnant women. All adverse outcomes of pregnancy studied were more frequent in SLE women without anti-PRL autoantibodies than anti-PRL autoantibody-positive SLE women. Moreover, both maternal and fetal main complications were significantly higher in SLE women without anti-PRL autoantibodies than anti-PRL autoantibody-positive SLE women (P

Possible interplay between vitamin C deficiency and prolactin in pregnant women with premature rupture of membranes: facts and hypothesis.

The precise etiologic mechanisms involved in the premature rupture of membranes (PROM) during pregnancy, the main cause of preterm delivery worldwide, are unknown. Previous studies have shown that: (a) the rupture of chorioamniotic membranes is related to an imbalance between synthesis and degradation of collagen induced by the overexpression/activity of various matrix metalloproteinases (MMP); (b) during human labor and delivery the expression of prolactin receptors (PRL-R) increases in chorioamniotic membranes, decidua and placenta; (c) prolactin (PRL) can influence the synthesis of prostaglandins, the expression of some MMP (MMP-2, MMP-9 and decysin) and tissue inhibitors of MMP in general; (d) vitamin C deficiency induces the expression/activity of extracellular MMP and is considered a risk factor for PROM; and (e) vitamin C potentiates the dopamine-mediated inhibition of PRL in rats. The present hypothesis proposes that a decreased hypothalamic dopaminergic tone-and thus an increased synthesis/release of pituitary PRL - is induced by vitamin C deficiency below a critical threshold (<18 microg/10(8) leukocytes) and that both factors, in turn, would cause upregulation of the expression/activity of several MMP. The increased PRL concentrations (acting like a Th1-type cytokine) along with the overexpression of other proinflammatory cytokines would induce a premature switch from a favorable Th2-type immune response to a noxious Th1-type immune response in the intrauterine environment. This change, in conjunction with the upregulation of MMP-2 and MMP-9, would cause a premature imbalance between synthesis/degradation of collagen in chorioamniotic membranes (an "anticipation" of the normal parturition cascade?), which favors extracellular matrix degradation, proposed as the most relevant event in the genesis of PROM. This hypothesis represents a new dimension in the study of the etiology of PROM.

The possible role of prolactin in preeclampsia: 2001, a hypothesis revisited a quarter of century later.

A genetic predisposition (theory 1) to preeclampsia in a woman with or without risk factors, may lead to an immune maladaptation to pregnancy (theory 2) (Th1 type of immune response predominance over Th2). In turn, they may contribute to an early defective 'switch' (quantitatively or out of timing) with a predominant decidual production of 16-kDa PRL over that of a 23-kDa PRL (our hypothesis), which induces an antiangiogenic process with a shallow invasion of the spiral arteries by the endovascular cytotrophoblast. Afterwards, a high-resistance arteriolar system and placental ischemia or hypoxia ensue, leading to endothelial cell dysfunction (theory 3) and an increased oxidative stress (theory 4). We are not proposing any strict chronological sequence of events, but the early occurrence (first 10 weeks) during pregnancy of the predominant decidual secretion of a 16-kDa PRL over that of 23-kDa PRL inducing a defective angiogenic process. No other specific mechanism(s) to explain the 'shallow' invasion of the spiral arteries has been previously proposed. Furthermore, it seems to happen early enough in pregnancy, as a 'very early change which may give a clue to the etiology,' as first suggested 25 years ago by Horrobin.

Decreased dopaminergic tone and increased basal bioactive prolactin in men with human immunodeficiency virus infection.

OBJECTIVE: The aims of the study were: (1) to assess dopaminergic tone in a group of HIV infected men and the bioactivity and the molecular species of their circulating PRL in comparison with healthy men and (2) to search for a correlation between serum PRL and CD4+ T lymphocytes and viral load. DESIGN: In a cross-sectional study the effect of acute dopaminergic blockade with intravenous metoclopramide on serum PRL (both immunoreactive and biologically active), TSH and PRL circulating molecular isoforms was evaluated. PATIENTS: Twenty untreated HIV infected men category C2 or C3, mean (SD) age 26.9 (6.3) years, were compared to 14 clinically healthy HIV-negative men, age 25.4 (2.3) years. MEASUREMENTS: Under fasting conditions and following metoclopramide administration duplicate measurements of serum immunoreactive PRL, bioactive PRL (PRL dependent Nb2 lymphoma cell assay) and immunoreactive TSH were performed. The molecular species of circulating PRL were determined by immunoblot analysis, CD4+ T lymphocytes by flow cytometry and the viral load using a nucleic acid sequence-based amplification assay. RESULTS: In HIV infected men fasting bioactive (but not immunoreactive) PRL was higher (P = 0.03), but the stimulated PRL (both immunoreactive and bioactive) was lower than in healthy men throughout the test (P < or = 0.01). Fasting serum TSH was similar in HIV-infected and healthy men while its response to metoclopramide was absent in the former but not in the latter (P = 0.049). A 23.5-kD PRL was the predominant circulating isoform both in patients and healthy men. Considering HIV-infected and healthy men, CD4+ T lymphocytes correlated negatively with fasting bioactive PRL (P = 0.008) and positively with the area under the PRL (both immunoreactive and bioactive) curves (P < 0.001). The viral load was negatively correlated with the area under the curve of the bioactive/immunoreactive ratio (P = 0.008). CONCLUSIONS: The raised fasting bioactive PRL, the diminished response of both immunoreactive and bioactive PRL and the absent TSH response to metoclopramide in HIV infected men, suggest the existence of a decreased, but not absent dopaminergic tone. A monomeric form of PRL was the predominant circulating species, as in healthy men, and this hormone seems to be associated both with CD4+ T lymphocytes and the viral load.

Serum prolactin is associated with apoptosis in men with human immunodeficiency virus infection.

We examined the in vivo and in vitro production of prolactin (PRL) in 20 untreated HIV-infected men compared to 14 uninfected men and its association with the cell cycle and apoptosis. Compared to uninfected men, the HIV-infected men had: (i) higher fasting serum bioactive (BIO) PRL; (ii) lower serum immunoreactive (RIA) and BIO-PRL responses to intravenous metoclopramide; (iii) greater BIO-RIA PRL ratio both fasting and during intravenous metoclopramide; (iv) lower percentage of non-stimulated PBMC in the G0/G1 phase, but a higher percentage in the S phase, of the cell cycle with normal response to Concanavalin-A; and (v) higher in vitro production of BIO-PRL by non-stimulated PBMC, which was blocked after Concanavalin-A. Fasting serum BIO-PRL positively correlated with the percent of non-stimulated PBMC in S + G2/M phases. The percentage of apoptotic PBMC negatively correlated with CD4+ T lymphocytes and with the area under the serum RIA-PRL curve, but positively correlated with the area under the curve for the BIO/RIA ratio. These results suggest that in these HIV-infected men: (i) a diminished dopaminergic tone may exist, as an adaptive mechanism attempting to survive; and (ii) BIO-PRL may participate as a cofactor in the stimulation of T-cell proliferation.

Thyroid peroxidase antibodies in Mexican-born healthy pregnant women, in women with type 2 or gestational diabetes mellitus, and in their offspring.

OBJECTIVE: To search for differences in the frequency of thyroid peroxidase antibodies (TPO-Ab) among 150 pregnant Mexican women who were healthy, had type 2 diabetes mellitus (DM), or had gestational diabetes mellitus (GDM). METHODS: Fifty healthy women, 50 women with type 2 DM, and 50 women with GDM were studied at delivery. In addition, 142 of their offspring were included in the study. TPO-Ab were determined by enzyme immunoassay, and total triiodothyronine, free thyroxine, and thyroid-stimulating hormone (thyrotropin) were measured by radioimmunoanalysis. RESULTS: TPO-Ab were < or = 70 U/mL (negative) in 50% of the healthy women and in 60% and 60% of women with type 2 DM and GDM, respectively (no significant difference). TPO-Ab were 71 to 250 U/mL (slightly positive) in 40% of healthy women and in 30% and 34% of women with type 2 DM and GDM, respectively (no significant difference). TPO-Ab were > or =251 U/mL (strongly positive) in 10% of healthy women and in 10% and 6% of women with type 2 DM and GDM, respectively. One healthy woman had subclinical hypothyroidism, and the rest were euthyroid. The newborn offspring of these Mexican women were euthyroid and had similar frequencies of TPO-Ab (all had TPO-Ab <250 U/mL). CONCLUSION: (1) The frequency of TPO-Ab > or =251 U/mL was similar in pregnant Mexican women with GDM in comparison with those who were healthy or had type 2 DM. (2) The similar high frequencies of slightly positive TPO-Ab in the three groups of pregnant women can partially be explained by the existence of an ethnic factor, the very strong family history of DM in a substantial percentage of them, and the use of a more sensitive and specific assay for detection of TPO-Ab.

Impaired metoclopramide-induced pituitary prolactin release in men with human immunodeficiency virus infection.

To investigate whether metoclopramide-induced prolactin release is impaired in HIV-infected men, we studied 10 clinically healthy HIV-negative adult men (group 1) and 10 consecutive HIV-positive adult men (group 2) with anti-HIV antibodies confirmed by Western blot analysis and a CD4 cell count from 13 to 570x10(6)/L. After a 10- to 12-hour overnight fast, three basal blood samples were obtained at 15-minute intervals (-30, -15, and 0 minutes) and thereafter at 15, 30, 60, 90, 120, 180, and 240 minutes after a 10-mg intravenous bolus of metoclopramide. Duplicate serum prolactin concentrations were measured in each sample with commercially available radioimmunoassay kits. No significant differences between groups were observed in basal prolactin levels. Group 2 had lower serum prolactin concentrations than group 1 throughout the test (P< or =.002). The area under the prolactin curve (mean +/- SD) was also lower in group 2 than in group 1 (7156+/-1433 ng/mL/240 min vs. 12430+/-2454 ng/mL/240 min, P<.0001), and the area under the prolactin curve had a significant correlation with the CD4 cell counts (r = 0.7912, P<.001). These findings suggest that the hypothalamic dopaminergic tone, although present, was clearly diminished in these HIV-positive men regardless of their clinical stage.

The uncoupled couple? Prolactin and CD4 lymphocytes in HIV infection.

The possible role of prolactin (PRL) in human immunodeficiency virus (HIV) infection is unknown, despite the modulatory role of this hormone in humoral and cell-mediated immune responses. Recent studies have evidenced: (a) intralymphocyte synthesis of dopamine (DA) which down-regulates their own proliferation and differentiation; (b) decreased DA but increased PRL concentrations in cerebrospinal fluid of HIV-infected men; and (c) diminished hypothalamic DA tone in HIV-infected men. The present hypothesis proposes that, in HIV-infected men, a diminished generalized DA tone exists to stimulate human lymphocyte proliferation and differentiation at a maximum possible rate by: (1) decreasing the inhibitory influence of intralymphocyte DA; and (2) maintaining pituitary and extrapituitary (i.e. lymphocyte) PRL synthesis and release as high as possible. If this hypothesis is correct, it may have a potentially important therapeutic implication: the possibility to rebuild the battered immune system in HIV-infected patients from inside the body in a physiologic manner by the parenteral administration of recombinant human PRL.

[Recurrent fetal death and antiphospholipid antibody syndrome. A case report]. / Muerte fetal repetida y síndrome de anticuerpos antifosfolípidos. Presentación de un caso.

Antiphospholipid Antibodies has been associated with severe maternal and fetal sequels, like recurrent miscarriage, death, intrauterine growth retardation, pregnancy-induced hypertensive disease, thromboembolic phenomena and thrombocytopenia. Pathogenesis has been explained reporting that IgG from women with antiphospholipid antibodies increases placenta thromboxane production without affecting prostacyclin production, which conducts to thrombosis of placenta uterus junction. In 1982, it was suggested for the first time low doses of aspirin and prednisone for treatment of recurrent fetal death associated to this syndrome, heparin therapy was reported in 1984, recommended a doses of 15,000 U/day during first pregnancy trimester and 20,000 U/day posteriorly. The objective of this report, is the description a clinic case of a patient with recurrent fetal death and antiphospholipid antibodies syndrome, discussing a prenatal and obstetric treatment model, including diagnosis and final therapeutic, which includes the participation of some other specialists, the national experience in diagnosis and treatment is initial, and also because it has been reported a rate of fetal death in those patient with no treatment, almost of 90%. The importance of identify this syndrome is not based on its prevalence but on its maternal complications and that it is a cause of fetal death potentially treatable.