Urinary concentration of Cathepsin D as a relievable marker of preeclampsia.

BACKGROUND: The early and accurate diagnosis of preeclampsia is crucial to avoid serious complications for both the mother and baby. However, the current diagnostic methods are limited, and there is a need for new diagnostic biomarkers. Previous studies have shown that cathepsin D (CTD) participates in the pathophysiology of preeclampsia and is present in urine samples, making it a potential biomarker for the disease. This study aimed to compare urinary and serum levels of CTD in preeclamptic and normotensive women and analyze its potential role as a diagnostic biomarker in preeclampsia. METHODS: The study included thirty-nine patients with preeclampsia and twelve normotensive pregnant women as controls. Biomarkers were determined using Multiplex Assay kit, and serum prolactin (Prl) and urinary TNF-α levels were also evaluated. Statistical analysis was conducted using the Mann-Whitney U test. RESULTS: We found that urinary and serum CTD levels were significantly higher in the preeclampsia group than in the normotensive group, suggesting that CTD could be a diagnostic biomarker for preeclampsia. No significant differences were found in the levels of serum prolactin or urinary TNF-α between the two groups. CONCLUSIONS: The study provides evidence that non-invasive biological samples such as urine can be used to improve new therapeutic strategies for the early management of preeclampsia.

Effect of manganese on neural endocrine hormones in serum of welders and smelters.

BACKGROUND: Although manganese (Mn)-induced neurotoxicity effects are well known among occupational Mn exposure, few reports have investigated the effects on endocrine systems among welders and smelters. OBJECTIVE: To determine the effect of high level occupational manganese (Mn) exposure on neuropsychological parameters and hormonal status. METHODS: We used a cross-sectional design with 52 welders, 48 smelters and 43 age-matched office workers from the same factory in China. We analyzed serum endocrine hormones level and airborne Mn concentrations. Erythrocyte and urine Mn levels were quantified using inductively-coupled plasma atomic emission spectroscopy. RESULTS: The geometric mean of air Mn concentrations for the welders and smelters were 19.7 and 273.1 µg/m3, respectively. Mn concentrations in erythrocytes of smelters were markedly greater than those in controls and welders, but there was no difference between the erythrocytes Mn levels of Control and welders. We also found an increase of Mn levels in the urine of both welders and smelters vs. controls; Mn levels in urine of smelters were higher than in welders. Self-reported neurobehavioral symptoms were higher in welders and smelters than in controls. Finally, thyroid-stimulating hormone (TSH) levels of welders were significantly lower than in controls, whereas smelters had lower prolactin (PRL), testosterone (TST) and follicle-stimulating hormone (FSH) concentrations than either controls or welders. CONCLUSIONS: These results show that smelters have higher Mn exposure than do welders, and that Mn levels in erythrocytes or urine can be a marker for exposure. Moreover, high level occupational Mn exposure increases adverse neurobehavioral effects, and also may disrupt endocrine systems.

Early pregnancy protein multiplex screening reflects circulating and urinary divergences associated with the development of preeclampsia.

BACKGROUND: Preeclampsia, a pregnancy disorder characterized by hypertension and proteinuria, represents the leading cause of fetal and maternal morbidity and mortality in developing countries. The identification of novel and accurate biomarkers that are predictive of preeclampsia is necessary to improve the prognosis of patients with preeclampsia. OBJECTIVE: To evaluate the preeclampsia predictive value of 34 angiogenic-related proteins. METHODS: We performed a nested cohort case-control study of pregnant women. The profile of the 34 proteins was evaluated at 12, 16, and 20 gestational weeks (GWs), using urine/plasma from 16 women who developed preeclampsia and 20 normotensive pregnant controls by Bio-Plex ProTM Human Cancer Biomarker Panels 1 and 2. RESULTS: The urine concentration of soluble epidermal growth factor receptor (sEGFR), hepatocyte growth factor (HGF), angiopoietin-2 (ANG-2), endoglin (ENG), soluble fas ligand (sFASL), interleukin 6 (IL-6), placental growth factor (PLGF), and vascular endothelial growth factor A (VEGF-A) at 12 GW, prolactin (PRL), ANG-2, transforming growth factor alpha (TGF-α), and VEGF-A at 16 GW, and soluble IL-6 receptor alpha (sIL-6Rα), ANG-2 and sFASL at 20 GW, were different between groups (p < 0.05). The concentration cut-off values calculated in this study for the mentioned proteins, predicted an increased risk to developing preeclampsia in a range of 3.8-29.8 times in the study population. CONCLUSION: The proteins sEGFR, HGF, ANG-2, sFASL, IL-6, PLGF, VEGF-A, PRL, TGF-α FGF-b, sHER2/Neu sIL-6Rα, ENG, uPA, and insulin-like growth factor binding protein 1 (IGFBP-1), were predictive of the development of preeclampsia and their use as markers for this disease should be considered.

High Prolactin Excretion in Patients with Diabetes Mellitus and Impaired Renal Function.

BACKGROUND: The metabolic clearance of prolactin (PRL) is partially executed by the kidney. Here, we investigate the urine excretion of PRL in patients with Diabetes Mellitus and renal impairment. METHODS: Serum and urine samples were collected from male, mestizo patients in central Mexico employing a cross-sectional study design. Ninety-eight individuals had either no diabetes and normal renal function (control), diabetes and normal renal function, or diabetes with impaired renal function. PRL was determined by a chemiluminescent immunometric assay; protein, albumin, and creatinine were evaluated using quantitative colorimetric assays. The results were analyzed using ANOVA-testing. RESULTS: Patients with Diabetes Mellitus and renal impairment had significantly higher urine PRL levels than patients with Diabetes Mellitus and normal renal function and control patients. Higher urine PRL levels were associated with lower glomerular filtration rates, higher serum creatinine, and higher urinary albumin-to-creatinine ratios (UACR). Urine PRL levels correlated positively with UACR. Serum PRL levels were similar among groups. CONCLUSIONS: Patients with Diabetes Mellitus and impaired renal function demonstrate a high urinary PRL excretion. Urinary PRL excretion in the context of proteinuria could contribute to PRL dysregulation in renal impairment.

Urinary nickel and prolactin in workers exposed to urban stressors.

The aim of our study is to verify whether the exposure to low Ni doses in urban air may have some effects on the prolactin values of outdoor workers exposed to urban pollutants. 334 workers have been included in the study and divided on the basis of gender, job, age, length of service and smoking habits. Each worker underwent urinary Ni and prolactin sampling. The t-test for independent samples, the Mann-Whitney U test for two mode variables (gender, smoking habit), the univariate ANOVA test and the Kruskal Wallis test for the variables in more than two modes (age, length of service and job duties) were performed on the total sample. Pearson's correlation coefficient (p two-tailed) among the parameters was evaluated both in the total sample and after the stratification by gender, smoking habit and job. Multiple linear regression was performed after taking account of the major confounding factors on the total sample and on the subcategories. The statistical tests showed a significant correlation between urinary Ni and prolactin both in the total sample and in the subcategories. We believe that the occupational exposure to low doses of Ni present in urban pollution may influence the prolactin values in exposed workers.

Circulating angiogenic factors and urinary prolactin as predictors of adverse outcomes in women with preeclampsia.

Preeclampsia is characterized by an imbalance in angiogenic factors. Urinary prolactin (PRL) levels and its antiangiogenic PRL fragments have been associated with disease severity. In this study, we assessed whether these biomarkers are associated with an increased risk of adverse maternal and perinatal outcomes in preeclamptic women. We studied 501 women with preeclampsia attended at a tertiary care hospital. Serum concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng), as well as urinary PRL levels, were measured by enzymed-linked immunosorbent assay. Antiangiogenic PRL fragments were determined by immunoblotting. The risk for any adverse maternal outcome and for having a small-for-gestational-age infant was higher among women with sFlt-1/PlGF ratios, sEng, and urinary PRL level values in the highest quartile (odds ratios ≥ 2.7), compared with the lowest quartile. Both urinary PRL levels and the presence of antiangiogenic PRL fragments were more closely associated with the risk of specific adverse maternal outcomes (placental abruption, hepatic hematoma or rupture, acute renal failure, pulmonary edema, maternal death, and need for endotracheal intubation, positive inotropic drug support, and hemodialysis; odds ratios ≥ 5.7 and ≥ 4.7, respectively) than either sFlt-1/PlGF ratio or sEng alone. We concluded that in preeclamptic women at the time of initial evaluation, sFlt-1/PlGF ratio and sEng are associated with increased risk of combined adverse maternal outcomes. However, urinary PRL concentrations and its antiangiogenic fragments appear to be better predictors of an adverse maternal outcome and may be useful for risk stratification in preeclampsia.

Characterization of the estrous cycle in female beluga (Delphinapterus leucas) using urinary endocrine monitoring and transabdominal ultrasound: Evidence of facultative induced ovulation.

Recent, successful application of assisted reproductive technologies in captive beluga has resulted from the extensive study of male beluga reproductive biology. Optimization of assisted reproduction requires additional detailed knowledge of the female estrous cycle. Our specific objectives were to: (1) validate urinary immunoassays for use in this species; (2) elucidate annual ovarian cycle dynamics through the combined use of hormone excretion patterns and transabdominal ultrasound; and (3) establish whether ovulation in this species is spontaneous or induced by male factors. Ovulation was observed in four of 15 estrous cycles monitored in four adult female beluga maintained in a single-sex group. After introduction of a breeding male, ovulation was observed in six of seven estrous cycles. All estrous cycles occurred from March through June. For spontaneous ovulations (n=4), the inter-estrous interval was 34d (range 33-35d), with a follicular phase length (FPL) of 25±8d (mean±SD). For all ovulatory estrous cycles (with and without a breeding male), urinary estrogen conjugates (EC, 15.3±7.9ng/mg Cr) and ovulatory luteinizing hormone (ovLH, 17.1±6.6ng/mg Cr) concentrations both peaked on Day 0, and EC concentrations returned to baseline 8±7d later. For non-conceptive cycles, urinary progestagen (Pg) concentrations increased on Day 0 (3.5±1.7ng/mg Cr), peaked on Day+19 (19.7±17.1ng/mg Cr), and were elevated above baseline for 27±4d. Preovulatory follicular diameter and circumference on Day -2±2 (range: Day -4 to -1) from peak EC were 2.5±0.7 and 7.8±1.3cm, respectively. The FPL in non-ovulatory estrous cycles (n=11) lasted 24±10d and EC concentrations gradually declined to baseline over a 21±10d interval following the EC peak (27.8±28.8ng/mg Cr). Non-ovulatory estrous cycles were characterized by the absence of an ovLH surge and no concomitant increase in Pg concentrations above baseline excretion; the mean follicular diameter at or near peak EC was 3.1±0.8cm on Day 2 ±3d from peak EC (range: -1 to +5days from peak EC). Overall, these data confirm that captive beluga exhibit reproductive seasonality and demonstrate that the species is a facultative-induced ovulator.

Assessment of luteinizing hormone and prolactin immunoactivity in Asian and African elephant urine using assays validated for serum.

Analysis of serum hormones is useful for timing artificial insemination (Luteinizing hormone) and diagnosing pregnancy (prolactin) in elephants. However, these tests require blood collection, which is not tolerated by all animals, and is impractical for field studies. Thus, developing a means to obtain these measures noninvasively could improve species management. Matched urine and serum was collected from Asian and African elephants daily throughout the follicular phase and after administration of a GnRH analogue for LH determination, and in pregnant and nonpregnant females for prolactin analyses using immunoassays validated for elephant serum. Despite identifying robust increases in circulating hormone concentrations, no concomitant changes in urinary LH or prolactin immunoactivity was detected. Concentration of samples by centrifugal filtration or ethanol precipitation did not increase the ability to measure biologically relevant changes in endogenous urinary LH or prolactin immunoactivity. Sample matrix interference was ruled out following sufficient recovery of exogenous LH or prolactin added to samples, except for samples concentrated >35-fold where some interference was suspected. These results suggest that elephants either do not excrete native LH or prolactin in urine, or concentrations are too low to be measured accurately by standard immunoassay techniques that are valid for serum analyses. Thus, it does not appear feasible or economically viable to use these noninvasive tests for ovulation detection or for pregnancy diagnosis in elephants.

Urinary prolactin as a reliable marker for preeclampsia, its severity, and the occurrence of adverse pregnancy outcomes.

CONTEXT: It has been proposed that preeclampsia may result from of an imbalance in angiogenic factors. Although prolactin (PRL) is mainly related to lactation, it is also involved in other biological functions, including angiogenesis. OBJECTIVE: Our objective was to determine the relationship among preeclampsia, serum and urinary PRL (uPRL) levels, and excretion of antiangiogenic PRL fragments in urine. STUDY DESIGN: Using a cross-sectional design, uPRL and serum PRL levels, and the presence of PRL isoforms were determined in 546 pregnant women: 207 healthy pregnant, 124 with gestational hypertension, 48 with mild preeclampsia, and 167 with severe preeclampsia (sPE). RESULTS: uPRL concentrations were significantly (P < 0.001) higher in preeclampsia (11.99 ng/mg creatinine) than in healthy pregnancy (0.20 ng/mg creatinine) and gestational hypertension (0.19 ng/mg creatinine), and were even higher in sPE compared with mild preeclampsia (21.20 vs. 2.77 ng/mg creatinine, respectively; P < 0.001). Antiangiogenic PRL fragments (14-16 kDa) were detected in 21.6% of urine samples from women with sPE but in none from other groups. Patients with hemolysis, elevated liver enzymes, low platelet count syndrome, and/or eclampsia, placental abruption, acute renal failure, and pulmonary edema exhibited highest uPRL concentrations (P < or = 0.028) and frequency of antiangiogenic PRL fragments in urine (P < or = 0.036). High-serum PRL levels were associated with sPE independently of gestational age, proteinuria, and prolactinuria (P = 0.032). CONCLUSIONS: Preeclampsia is characterized by increased uPRL excretion. uPRL concentrations and their isoforms appear to be suitable markers to assess the severity of preeclampsia and occurrence of adverse outcomes. PRL and and/or its isoforms might be involved in the pathophysiology of preeclampsia.

Effect of constant light on prolactin and corticosterone rhythms evaluated using a noninvasive urine sampling protocol in the rat.

Circadian prolactin and corticosterone rhythms are usually investigated in the rat by analysis of plasma hormone profiles. In order to develop a nonstressful methodology for long-term studies, we validated prolactin and corticosterone radioimmunoassays in rat urine samples. Among the criteria of validation, prolactin was identified in urine by Western blot whereas both prolactin and corticosterone levels were undetectable in the urine of hypophysectomized rats. The determination of prolactin and corticosterone levels on serial urine samples showed daily variations in male rats entrained by the light-dark cycle. The acrophases of the 24-hour prolactin and corticosterone profiles were located at 03:26 h and 23:32 h respectively, a delay of 3-4 hours compared with the values of the 24-hour plasma profiles reported in the literature. Corticosterone and prolactin rhythms were abolished or dramatically delayed after 3 weeks of constant illumination. As expected, constant light suppressed the rhythm of 6-sulfatoxymelatonin, the major hepatic metabolite of melatonin. The noninvasive and nonstressful methodology we developed could be of interest for studying the regulation of hormone rhythms and their mutual endocrine interactions in physiological conditions, especially their evolution in the aging process.

Changes in prolactin and glucocorticoid levels in cotton-top tamarin fathers during their mate's pregnancy: the effect of infants and paternal experience.

We have previously shown that paternally experienced cotton-top tamarin fathers (Saguinus oedipus) had significant increases in prolactin and glucocorticoids at the midpoint of their mate's pregnancy, whereas less experienced fathers showed prolactin increases only the month before offspring birth [Ziegler & Snowdon, Hormones & Behavior 38:159-167, 2000; Ziegler et al., Hormones & Behavior 45:84-92, 2004]. These results could be owing to differing paternal experience or from paternal care given to previous offspring. To test the relative role of infant cues and paternal experience in these hormonal changes, we paired four paternally experienced tamarin fathers with a novel, primiparous female and monitored hormone levels during their first pregnancy together. No fathers showed the significant mid-pregnancy increase in prolactin seen previously. However, all fathers showed increases in cortisol and significant peaks of corticosterone in mid-pregnancy. The increase in corticosterone was consistent with previous data occurring in each male during the same week or the week following the urinary cortisol increase shown by his mate. These data may suggest that the elevated mid-gestation prolactin seen previously in experienced males may be owing to the presence of offspring from the previous set of infants. In contrast, increased cortisol and corticosterone occurred independently of infant cues and may be related to previous paternal experience. We therefore conclude that both offspring presence and paternal experience contribute to the hormonal changes seen in experienced cotton-top tamarin fathers during their mate's pregnancy.

Elevated vasoinhibins may contribute to endothelial cell dysfunction and low birth weight in preeclampsia.

Vasoconstriction and defective placental angiogenesis are key factors in the etiology of preeclampsia. Prolactin levels are elevated in maternal blood throughout pregnancy and the human decidua produces prolactin that is transported to the amniotic fluid. Prolactin is cleaved to yield vasoinhibins, a family of peptides that inhibit angiogenesis and nitric oxide-dependent vasodilation. Here, we conducted a case-control study to measure vasoinhibins in serum, urine, and amniotic fluid obtained from women with severe preeclampsia. We show that all three biological fluids contained significantly higher levels of vasoinhibins in preeclamptic women than in normal pregnant women. Amniotic fluid from preeclamptic women, but not from normal women, inhibited vascular endothelial growth factor-induced endothelial cell proliferation and nitric oxide synthase activity in cultured endothelial cells, and these actions were reversed by antibodies able to neutralize the effects of vasoinhibins. Furthermore, amniotic fluid does not appear to contain neutral prolactin-cleaving proteases, suggesting that vasoinhibins in amniotic fluid are derived from prolactin cleaved within the placenta. Also, cathepsin-D in placental trophoblasts cleaved prolactin to vasoinhibins, and its activity was higher in placental trophoblasts from preeclamptic women than from normal women. Importantly, birth weight of infants in preeclampsia inversely correlated with the extent to which the corresponding AF inhibited endothelial cell proliferation and with its concentration of prolactin+vasoinhibins. These data demonstrate that vasoinhibins are increased in the circulation, urine, and amniotic fluid of preeclamptic women and suggest that these peptides contribute to the endothelial cell dysfunction and compromised birth weight that characterize this disease.

Urinary prolactin is correlated with mothering and allo-mothering in squirrel monkeys.

The hormone prolactin is implicated in infant care-giving by parents and allo-parents in a variety of species. Adult female squirrel monkeys (Saimiri spp.) engage in allo-mothering behavior, which includes carrying and nursing infants, but communal care of offspring has not been investigated from an endocrine standpoint in this taxon. We attempted to fill this gap by examining prolactin levels in squirrel monkeys (Saimiri sciureus) as a function of parental responsiveness. Subjects were housed at the National Institutes of Health Animal Center and assays were performed at the Wisconsin National Primate Research Center. To test for the presence of prolactin in squirrel monkey, saliva, blood and saliva were simultaneously collected from anesthetized subjects during routine health examinations. Prolactin was detectable in serum but not in saliva samples. In the core investigation, behavioral data were collected by focal animal sampling on three 1-male multi-female groups, and individually identified urine was collected non-invasively from foil containers underneath group cages on a daily basis throughout the behavioral study. Changes in urinary prolactin over time reflected changes in the reproductive state of a female who was pregnant, gave birth and lactated during the study. Mean urinary prolactin levels in non-lactating females and a male housed with infants in one group were higher than in adults from 2 groups without infants. In the group with infants, mean urinary prolactin levels in adults increased with the amount of infant contact and care-giving. The squirrel monkey may represent a new primate model for investigating the endocrinology of infant care-giving.

Development of prolactin levels in marmoset males: from adult son to first-time father.

Previous studies have found a clear relationship between prolactin (prl) and paternal care in various vertebrate taxa. In New World monkeys, it has been demonstrated in several species that fathers have high prolactin levels even during periods without infant rearing. In this study, we followed the reproductive careers of common marmoset males as they transitioned from being an adult son within their native family to fathering their own offspring for the first time. Specifically, we examined the first experience of elevated prolactin levels in marmoset males. Additionally, we investigated the effects of the total number of experienced births as well as of age on prolactin levels. Our results show that common marmoset males did not experience an increase in prolactin secretion after pairing or shortly before birth of their first infants. However, prolactin levels rose more than twofold after the birth of their first infants and had lowered again 2.5 months after this event. We found no correlation between prolactin levels and the number of previous births experienced or age. Our study demonstrates that further work about a possible enhancing effect of prolactin on paternal care, by means of experimentally reducing hormonal levels, should be conducted in common marmosets using first-time fathers before males experience the first paternal increase in prolactin levels.

Relationship of serum prolactin with severity of drug use and treatment outcome in cocaine dependence.

RATIONALE: Alteration in serum prolactin (PRL) levels may reflect changes in central dopamine activity, which modulates the behavioral effects of cocaine. Therefore, serum PRL may have a potential role as a biological marker of drug severity and treatment outcome in cocaine dependence. OBJECTIVE: We investigated whether serum PRL levels differed between cocaine-dependent (CD) subjects and controls, and whether PRL levels were associated with severity of drug use and treatment outcome in CD subjects. METHODS: Basal PRL concentrations were assayed in 141 African-American (AA) CD patients attending an outpatient treatment program and 60 AA controls. Severity of drug use was assessed using the Addiction Severity Index (ASI). Measures of abstinence and retention during 12 weeks of treatment and at 6-month follow-up were employed as outcome variables. RESULTS: The basal PRL (ng/ml) in CD patients (9.28+/-4.13) was significantly higher than controls (7.33+/-2.94) (t=3.77, P<0.01). At baseline, PRL was positively correlated with ASI-drug (r=0.38, P<0.01), ASI-alcohol (r=0.19, P<0.05), and ASI-psychological (r=0.25, P<0.01) composite scores, and with the quantity of cocaine use (r=0.18, P<0.05). However, PRL levels were not significantly associated with number of negative urine screens, days in treatment, number of sessions attended, dropout rate or changes in ASI scores during treatment and at follow-up. Also, basal PRL did not significantly contribute toward the variance in predicting any of the outcome measures. CONCLUSION: Although cocaine use seems to influence PRL levels, it does not appear that PRL is a predictor of treatment outcome in cocaine dependence.

Responsiveness of expectant male cotton-top tamarins, Saguinus oedipus, to mate's pregnancy.

In the cotton-top tamarin, a primate where paternal care is critical to the survival of the offspring, we found that expectant fathers experienced multiple hormonal changes during their mate's pregnancy. Fathers that had experienced several previous births showed significant changes in urinary estrogens, androgens, prolactin and cortisol in the last 2 months before birth, whereas less-experienced fathers (LEF) did not. The female's midpregnancy rise in glucocorticoids was followed within 1-2 weeks by a peak of cortisol and corticosterone in her paired male in 70% of all males and 100% of all experienced males. Examination of behavioral interactions between the pairs did not reveal changes in rates of interactions between the experienced pairs over pregnancy. However, the less-experienced pairs had significantly higher levels of affiliative and sexual interactions. Therefore, behavioral communication between the pair did not appear to account for the hormonal changes occurring within the experienced fathers (EF). The midpregnancy rise of glucocorticoids in females may stimulate a glucocorticoid response in male tamarins and thereby activate other hormonal changes in males to prepare them for their parenting role.

Prolactin and paternal care: comparison of three species of monogamous new world monkeys (Callicebus cupreus, Callithrix jacchus, and Callimico goeldii).

The authors explored whether prolactin is associated with paternal care in 3 monkey species: titi monkey (Callicebus cupreus), common marmoset (Callithrix jacchus), and Goeldi's monkey (Callimico goeldii). They compared prolactin levels in fathers before and after infant birth as well as between fathers and nonfathers. C. cupreus fathers carry infants almost exclusively, have higher prolactin levels than nonfathers, but show no prolactin increase after infant birth. C. goeldii fathers carry infants only after 3 weeks, show an increase in prolactin levels during the precarrying period, but do not have higher levels than nonfathers. C jacchus fathers are the primary carriers, have higher prolactin levels than nonfathers, and show a trend for a prolactin increase after the birth of infants. In conclusion, species differences in the patterns of prolactin secretion were evident and reflect the different paternal roles.

Male orangutan subadulthood: a new twist on the relationship between chronic stress and developmental arrest.

Both in the wild and in captivity, a marked and enduring arrest of secondary sexual developmental occurs in some male orangutans (Pongo pygmaeus) (Kingsley [1982] The Orang-Utan: Its Biology and Conservation, The Hague: Junk; Utami [2000]). Researchers have hypothesized that chronic stress, perhaps related to aggression from mature males, causes endocrine changes altering growth and maturation rates in these males (Maple [1980] Orangutan Behavior, New York: Van Nostrand Reinhold; Graham [1988] Orangutan Biology, Oxford: Oxford University Press). In this study, urine samples were collected over a 3-year period from 23 captive male orangutans to test the hypothesis that developmentally arrested male orangutans have an endocrine profile consistent with chronic stress. Three study males were juveniles, seven were arrested adolescents, six were developing adolescents, and seven were mature adults. Morning samples were analyzed by radioimmunoassay for levels of the stress hormones cortisol and prolactin, and group hormone profiles were compared by analysis of variance. Results indicate that developing adolescent male orangutans have a significantly higher stress hormone profile than juvenile, developmentally arrested adolescent, or adult males. These results imply that the arrest of secondary sexual development in some male orangutans is not stress-induced, but instead perhaps an adaptation for stress avoidance during the adolescent or "subadult" period. These data, together with previously reported data on levels of gonadotropins, testicular steroids, and growth-related hormones, define endocrine profiles associated with alternative reproductive strategies for males with and males without secondary sexual features (Maggioncalda et al. [1999], [2000].

Growth hormone hypersecretion in a girl with neurofibromatosis type 1 and an optic nerve glioma: resolution following chemotherapy.

Growth hormone hypersecretion is extremely rare in childhood. We report a girl with neurofibromatosis type 1, an extensive optic nerve glioma and growth hormone hypersecretion. She was treated with chemotherapy to prevent further extension of her sight-threatening tumour. Three years after chemotherapy her growth hormone hypersecretion has resolved although she has gone on to develop precocious puberty.

Clinical significance of serum and urine prolactin levels in lupus glomerulonephritis.

UNLABELLED: Prolactin (PRL) has been involved in the pathogenesis of systemic lupus erythematosus (SLE) and hyperprolactinemia has been connected with systemic activity. However, the clinical significance of PRL has not been investigated in lupus glomerulonephritis (GN). METHODS: We studied SLE patients (ACR criteria) with biopsy-proven renal disease. Renal histology was classified according to World Health Organization (WHO) criteria. Renal function tests, albuminuria, complement levels (nephelometry), anti-DNA antibodies (C. luciliae) and serum and urine PRL concentrations (RIA) were determined at baseline and at 4-month intervals for one year. Renal activity was defined as mild, moderate or severe according to serum creatinine, creatinine clearance, albuminuria, red blood cells (RBC), and casts. RESULTS: There were 26 patients with mean age 28.5 y and mean disease duration 47.9 months. Twenty patients had diffuse proliferative glomerulonephritis (GN), four had focal GN and two had membranous GN with proliferative changes. Renal activity was mild in ten patients, moderate in ten and severe in six. Mean serum (24.7+/-5.3) and urine (0.90+/-0.36) PRL levels were higher in patients with severe renal activity (P < 0.05 compared with mild group). PRL levels decreased after treatment, but this trend was not uniform during the follow-up period. CONCLUSION: Hyperprolactinemia was prevalent in SLE patients and high levels of PRL in the serum and urine could be related to severe renal disease.