Effect of prolactin suppression on gonadotrophic secretion in the puerperium

Serum levels of prolactin (PRL), FSH, LH and oestradiol-17 beta were determined by radioimmunoassay in 57 lactating women and in 20 women in whom lactation was inhibited by ergocryptine (CS-154). Women who breast fed their infants exhibited high PRL levels which abruptly declined within 48 h post-partum, and remained low for the duration of the study. Serum FSH was undetectable during the first week post-partum in lactating as well as in CB-154 treated women. Thereafter, lactating women showed increasing FSH levels which reached a maximum by the third week post-partum. These FSH values were higher in lactating women than in the CBS-154 treated group. In contrast, LH levels were higher in those women receiving CB-154. Serum oestradiol-17 beta remained in low levels throughout the study, and no difference was observed between the two groups of subjects. From these results it seems that: 1) inhibition of PRL secretion leads to a faster recovery of gonadotrophin secretion toward the "menstrual type", and 2) PRL suppression produces no effect on the ovarian oestrogen production.     

Prolactin and thyrotropin responses to thyrotropin-releasing hormone in patients with secondary amenorrhea: the effect of bromocriptine

Prolactin (PRL) and thyrotropin (TSH) responses to a 200 mug intravenous thyrotropin-releasing hormone (TRH) bolus were measured by radioimmunoassay in 11 women with hyperprolactinemic amenorrhea and 9 with normoprolactinemic amenorrhea. In all cases, the tests were carried out under basal conditions and repeated during bromocriptine treatment. In women whose basal PRL level was normal; TRH caused a maximal PRL increment of 85 +/- 25.2 mug/l (mean +/- SE), while those women whose basal PRL level was raised showed a smaller increase (5.2 +/- 11.9 mug/l) (P=0.02). The peak levels were not significantly different in these two groups (95.0 +/- 26.7 and 134.6 +/- 35.9 mug/l) (P is greater than 0.1). During bromocriptine treatment, the raised PRL levels decreased in all cases, but levels over 30 mug/l remained in 3 patients, one of whom turned out to have a pituitary tumor. Prolactin responses to TRH were markedly inhibited in normoprolactinemic patients by the dose of bromocriptine used. The mean maximal net increase of PRL was 2.0 +/- 0.9 mug/l in normoprolactinemic patients and 11.0 +/- 8.1 mug/l in hyperprolactinemic patients taking bromocriptine. After TRH stimulation during bromocriptine, the peak PRL levels in hyperprolactinemic patients were higher (32.7 +/- 10.5 mug/l) than in normoprolactinemic patients (7.2 +/- 1.5 mug/l). Unlike what has been described for hypothyroid patients, the basal TSH level in euthyroid amenorrhea patients was not affected by bromocriptine, and we found that bromocriptine has no effect on the TRH-TSH response.     

Prolactin bioactivity and the duration of lactational amenorrhea

In our population, only half of fully nursing women remain amenorrheic 6 months postpartum. The other half recover their menstrual cycles between 90-180 days postpartum in spite of a high suckling frequency and elevated immunoreactive PRL (IR-PRL) concentrations. To further investigate the association of PRL with the recovery of ovarian function, we compared PRL bioactivity (BIO-PRL) 3-4 months postpartum in fully nursing amenorrheic women who subsequently experienced long (> 180 days; n = 5) or short (< 180 days; n = 5) lactational amenorrhea. In the present study, BIO-PRL in plasma was measured by the Nb2 lymphoma cell assay in samples taken before and 30 min after a suckling episode at 0800, 1600 and 2400 h. Women in the long amenorrhea group had higher overall mean BIO-PRL (mean +/- SE, 129.9 +/- 12.1 micrograms/L) than nursing women in the short amenorrhea group (66.6 +/- 5.2 micrograms/L; P < 0.05). Mean basal values were similar, but the women in the long amenorrhea group had more BIO-PRL in response to suckling (160.1 +/- 4.0 vs. 71.9 +/- 6.7 micrograms/L; P < 0.05). Compared with their respective basal values, nursing women in the long amenorrhea group demonstrated increased BIO-PRL in response to suckling, whereas the other group did not. The relationships between BIO-PRL and IR-PRL were similar in the two groups of nursing women before suckling. However, after suckling, the long amenorrhea group had significantly higher BIO-PRL levels than IR-PRL levels (P < 0.05, by likelihood test) than the short amenorrhea group. This suggests that suckling differentially changes in each group either the composition of PRL present or substances that may modify the bioactivity of PRL in plasma.     

Reduced response of the hypothalamo-pituitary-adrenal axis to alpha1-agonist stimulation during lactation

To determine whether altered noradrenergic activation of the hypothalamo-pituitary-adrenal (HPA) axis contributes to the attenuated neuroendocrine response to stress observed during lactation, the effect of intracerebroventricular injection of the alpha1-agonist methoxamine (100 microg) was compared between virgin and lactating rats. Virgin rats showed significant increases in plasma corticosterone after methoxamine, reaching 317 +/- 44 ng/ml at 10 min and remaining significantly elevated for more than 120 min, but lactating rats showed no significant increase in corticosterone levels. Furthermore, methoxamine induced an increase in paraventricular nucleus (PVN) CRF messenger RNA expression in virgin, but not lactating, animals. Both groups of rats exhibited comparable elevations in plasma PRL after methoxamine treatment. Arginine vasopressin messenger RNA expression within the parvocellular PVN was greater in the lactating animals than in the virgin controls, but methoxamine injection was without further effect. Studies performed on ovariectomized virgin rats and ovariectomized rats receiving estradiol or progesterone replacement failed to reproduce the attenuated HPA responses seen after methoxamine treatment, although methoxamine-induced PRL levels were greatly increased by estradiol, probably arising from an effect on hormone synthesis. In vitro electrophysiological recordings of PVN neurons in hypothalamic slices from proestrous virgin and lactating rats showed that 45-52% of neurons in both groups exhibited excitatory responses to 10(-4) M methoxamine, but there was a differential response to 10(-5) M methoxamine, with PVN neurons from lactating animals failing to show a response. These data show a selective down-regulation of alpha1-mediated activation of the HPA axis in lactating animals. This may contribute to the attenuated stress-induced activation of the HPA axis during lactation.     

Effects of calcium supplementation and lactation on iron status

Calcium has been shown to inhibit iron absorption. The consequences of chronic calcium supplementation on iron status are unclear, however. As part of a randomized calcium-supplementation trial in lactating and nonlactating women in the postpartum period, we determined whether long-term calcium supplementation and lactation status affected iron stores as measured by serum ferritin concentrations. Subjects (95 lactating and 92 nonlactating) were enrolled at approximately 6 mo postpartum and then randomly assigned to receive either 500 mg Ca as calcium carbonate or a placebo twice daily with meals for 6 mo. Lactating women weaned their infants approximately 2 mo after enrollment (ie, approximately 8 mo postpartum). Calcium supplementation had no effect on serum ferritin concentrations. At the end of the study, geometric mean serum ferritin concentrations were 28.4 microg/L in the calcium-supplemented group and 27.5 microg/L in the placebo group (P > 0.5). Lactation status was significantly related to serum ferritin concentrations. At baseline, serum ferritin concentrations were higher in lactating women than in nonlactating women (47.7 compared with 31.5 microg/L, P < 0.001). In lactating women, serum ferritin concentrations decreased by a mean of 17 microg/L after weaning. By 12 mo postpartum, mean serum ferritin concentrations in women who were previously lactating were not significantly higher than those of nonlactating women (30.5 compared with 25.5 microg/L). These findings provide reassurance that long-term calcium supplementation does not impair iron stores. Furthermore, lactation status should be considered when assessing iron nutriture of women and determinants of iron status in populations.     

Intracellular staining of Purkinje cells and their axons with horseradish peroxidase

Neuroendocrine assessments were made in a 16-year-old girl with pseudocyesis of 38 weeks duration. Basal levels of pituitary LH and PRL, but not of FSH, were markedly elevated and the pulsatile pattern of LH and PRL appears to be exaggerated compared with those found in normal cycling women. Growth hormone levels were normal, with an appropriate increase after arginine infusion and l-dopa. The increased luteotropic action resulting from increased plasma LH and the lactogenic action of increased plasma PRL were associated with the presence of luteal function and galactorrhea. The dominant role of psychic mechanism(s) in causing hypersecretions of LH and PRL is suggested by the almost immediate fall in the serum concentrations and the rapid resolution of abdominal distention after the diagnosis was revealed to the patient.     

Inhibition of omeprazole induced hypergastrinaemia by SMS 201-995, a long acting somatostatin analogue in man

Whether the long acting somatostatin analogue SMS 201-995 (octreotide, Sandostatin) could inhibit the basal and meal stimulated hypergastrinaemia and hyperpepsinogenaemia induced by omeprazole was investigated. Eight healthy subjects were randomised to receive five day courses of SMS 201-995 (25 micrograms subcutaneously three times daily), omeprazole (40 mg once a day), a combination of both drugs, or placebo. Basal and meal stimulated serum gastrin and basal serum pepsinogen A and C values were measured the day before treatment, on day five of treatment, and the day after each course of treatment. Omeprazole caused significant increases in basal and meal stimulated peak and integrated serum gastrin values and pepsinogen A and C levels, which were still significantly raised the day after stopping omeprazole treatment. Giving SMS 201-995 with omeprazole significantly reduced any omeprazole induced increases in basal and meal stimulated peak and integrated serum gastrin levels; serum pepsinogen A and C values were significantly inhibited too. Serum gastrin values during combined therapy were not significantly different from those during placebo treatment, whereas pepsinogen A and C levels were still significantly raised. On the day after stopping combined therapy, basal and meal stimulated peak and integrated serum gastrin and serum pepsinogen C (but not pepsinogen A) levels were not significantly different from values obtained on the day after stopping omeprazole alone. SMS 201-995 without omeprazole significantly inhibited basal and meal stimulated peak and integrated serum gastrin levels. Pepsinogen A was also significantly inhibited by SMS 210-995, but the reduction in pepsinogen C failed to reach statistical significance. In conclusion, SMS 201-995 prevents basal and meal stimulated increases in serum gastrin during omeprazole therapy. This finding may have clinical importance in the few patients who have pronounced hypergastrinaemia because of profound long acting acid inhibition.     

mtDNA variation in caste populations of Andhra Pradesh, India

The aim of the study was to determine the association between PRL responses to suckling and maintenance of postpartum amenorrhea among breastfeeding mothers. Three blood spot samples (5, 30, and 50 min following a timed nursing bout) were collected from 71 intensively breastfeeding Nepali women for PRL determination. Maternal age, BMI (weight/height2), menstrual status, caste, infant age, nursing bout length, and duration of supplementation were recorded at time of sample collection. Independent and paired t tests, linear regression analyses, and general linear models were used to evaluate differences between cycling (n = 36) and amenorrheic (n = 35) women and associations among variables. Logistic regression analyses were used to relate PRL measures to the odds of maintaining lactational amenorrhea. Amenorrheic breastfeeding mothers had higher (P < .001) PRL levels at all 3 collection times than cycling breastfeeding mothers, and PRL levels declined with time since birth (P < 0.05). The odds (OR) of having ceased lactational amenorrhea was significantly higher (OR = 5.0, 95% Cl = 1.3-19.9) among mothers with lower PRL levels (< or = 10 ng/mL) at 50 min post-sucking, and PRL at 50 min showed a significant dose response relationship with menstrual status. The association between 50 min PRL levels and lactational amenorrhea appears to be independent of time postpartum, maternal age, BMI, nursing bout length, and duration of supplementation. Among intensively nursing women, maintenance of elevated PRL levels across the interbout interval increases the odds of maintaining lactational amenorrhea.     

Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study

Prolactinomas in women commonly present as small intrasellar tumors, but are usually much larger in men. This discrepancy has generally been attributed to differences in the delay before diagnosis. However, studies comparing clinical and pathological correlates of growth of these tumors in both sexes are lacking. We conducted a retrospective study comparing 45 men and 51 women bearing prolactinoma to determine whether the predominance of large tumors in men was due to a delay in diagnosis or, rather, to a fundamental sex-related difference in tumor growth. Basal PRL levels (mean +/- SEM, 2789 +/- 573 ng/mL) and mean tumor diameter (26 +/- 2 mm) were significantly higher in men than in women (292 +/- 74 ng/mL and 10 +/- 1 mm, respectively; P < 0.001), but were not correlated to the age at diagnosis or the duration of symptoms. Giant tumors (n = 8) occurred in males only. The frequencies of bromocriptine-resistant tumors (30 vs.5%; P < 0.01) and invasive macroadenomas (52 vs.27%; P < 0.001) were significantly greater in men than those in women. Lastly, macroprolactinomas in males exhibited higher indexes of proliferating cells by Ki-67 immunoreactivity (2.6 +/- 1.1% of positive nuclei) than did similar tumors in female patients (0.4 +/- 0.2%; P = 0.08). We conclude that the predominance of large prolactinomas in men is due to a high frequency of rapidly growing tumors, which are often invasive and frequently bromocriptine resistant.     

Leptin in human reproduction: serum leptin levels in pregnant and lactating women

Experiments in ob/ob female mice demonstrated that leptin injections not only reduced weight and fat mass, but also restored fertility and partial lactation. To explore factors regulating ob gene expression in reproductive women, we measured serum leptin, body fat, energy expenditure, and milk production in 65 women at 36 weeks of gestation, and at 3 and 6 months postpartum. Serum leptin was measured by solid-phase sandwich enzyme immunoassay, and serum insulin and PRL by solid-phase 125I RIA. Total body water by deuterium dilution, body volume by hydrodensitometry, and bone density by dual-energy x-ray absorptiometry were used to estimate body fat. Serum leptin per unit fat mass was significantly higher at 36 weeks of pregnancy than at 3 and 6 months postpartum (1.25 vs. 0.75, 0.73 ng.mL-1.kg-1). Postpartum normalization of leptin was associated with changes not only in weight and fat mass, but also serum insulin. Leptin was not different between lactating and nonlactating women. Leptin may have affected milk production indirectly through its negative effect on serum PRL. Adjusted for fat-free mass and fat mass, rates of energy expenditure were not significantly correlated with leptin. Our results provide evidence that factors other than fat mass alone modulate serum leptin in reproductive women.     

Circadian responsiveness of the hypothalamic-pituitary axis

Five healthy men 25-38 years old were subjected to simultaneous composite intravenous stimulation tests of insulin hypoglycemia (0.1 U/kg), thyrotropin-releasing hormone (TRH, 100 mug), and luteinizing hormone-releasing hormone (LHRH, 50 mug) at weekly intervals to study the circadian responsiveness of the hypothalamic-adenohypophyseal axis at 0600, 1200, 1800, and 0000 hours. Blood sugar (BS), LH, follicle-stimulating hormone, TSH, prolactin, cortisol (C), growth hormone, and testosterone (T) levels were estimated before and after the administration of drugs. Comparisons were made between basal and delta values (difference between basal and peak or nadir levels) at different tests. Significant circadian variations in BS, GH, C, and, to a lesser extent PRL, responses were observed 0600 h basal and delta BS values were the lowest, delta BS was highest at 0000 h accompanied by maximal hypoglycemic symptoms; the delta values of both C and GH were significantly higher at 0600 h and 0000 h; highest mean delta PRL was observed at 0600; at 1800 h the basal plasma PRL level was maximum but the delta PRL was lowest. Plasma TSH, LH, and FSH responses did not show significant circadian variations. These results suggest that circadian variations are evident when stimuli act through central or hypothalamic mechanisms; however, direct stimulation of the adenohypophysis resulted in indentical responses at different periods tested.     

Effects of lactation and lifestyles including food intake on bone density of lactating women

Ultrasonic bone densities were measured in 131 lactating women, aged 21 to 42 years, at 6-590 days postpartum. STIFFNESS Calculated from the combined value of speed of sound and broadband ultrasound attenuation at the calcaneus was used as an index of bone density. The relationships of STIFFNESS with period of lactation, current and past consumption of cow's milk, various food intake frequency, history of participating in sports, daily physical activity, using calcium drugs and sun exposure were examined using stepwise multiple regression analysis, including age and weight as independent variables. 1) The mean (SD) of STIFFNESS was 79.8 (11.9). Thirty-three women (25% of subjects) showed STIFFNESS less than 70. 2) Period of lactation showed a significant negative effect on STIFFNESS (p < 0.05). However, no such effect appeared for women with cow's milk intake of less than 100 ml per day. This result suggests a protection of calcium levels in bone. 3) Current daily cow's milk intake showed significant positive effect on STIFFNESS (p < 0.05). For women lactating less than 150 days, this relation between cow's milk intake and STIFFNESS was clear (r = 0.44, p < 0.01). 4) Significant relation between STIFFNESS and food intake frequencies was found in milk and milk products only among various foods. This result indicates that cow's milk and milk products are important sources of calcium during lactation.     

A further investigation of basal HPT axis function in unipolar depression: effects of diagnosis, hospitalization, and dexamethasone administration

Hypothalamic-pituitary-thyroid (HPT) axis function was assessed in depressed subjects 1 and 8 days after hospital admission, and after the administration of 1 mg of dexamethasone. Plasma levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured by ultrasensitive assays in 16 patients with minor depression, 15 patients with simple major depression, and 13 patients with melancholia. The postdexamethasone adrenocorticotropic hormone (ACTH) (intact 1-39 molecule) and cortisol values were determined. Basal TSH values were significantly lower in melancholic patients than in patients with minor and simple major depression on the day after admission and 1 week later. Basal TSH values determined 1 week after admission were significantly and negatively related to FT4 values and severity of depression. There were no significant differences in basal TSH, FT3, and FT4 values obtained on day 1 and day 8 after hospital admission. Dexamethasone administration had a significant suppressant effect on basal TSH and FT3 values. Patients who failed to suppress cortisol after the dexamethasone suppression test (DST) exhibited significantly less suppression of basal TSH values than did DST cortisol suppressors.     

Suppressive effect of calcium on parathyroid hormone release in adynamic renal osteodystrophy and secondary hyperparathyroidism

Serum parathyroid hormone (PTH) levels are markedly lower in patients with the adynamic lesion (AD) of renal osteodystrophy than in those with secondary hyperparathyroidism (2 degrees HPT), but serum PTH values are often moderately elevated in AD when compared to subjects with normal renal and parathyroid gland function (NL). To study the inhibitory effect of calcium on PTH release in AD and in 2 degrees HPT, the response to two-hour intravenous calcium infusions was examined in 6 patients with AD, in 31 patients with 2 degrees HPT and in 20 NL. Basal serum PTH levels were 88 +/- 51, 536 +/- 395, and 26 +/- 6 pg/ml, respectively, in AD, 2 degrees HPT and NL, whereas basal ionized calcium levels did not differ. When expressed as a percentage of pre-infusion values, PTH levels at the end of two-hour calcium infusions were higher both in AD (23.2 +/- 5.6%) and in 2 degrees HPT (27.8 +/- 12.3%) than in NL, (11.9 +/- 5.8%, P < 0.001). Both the amplitude of suppression (%) and the rate of decline (min-1) in serum PTH were less in AD and 2 degrees HPT than in NL, P < 0.05 for each parameter; corresponding values for each group, with 95% confidence intervals, were 77% (73 to 82) and 0.039 min-1 (0.030 to 0.048) in AD, 72% (68 to 76) and 0.031 min-1 (0.025 to 0.036) in 2 degrees HPT and 87% (84 to 89) and 0.070 min-1 (0.058 to 0.089) in NL. Neither variable differed between AD and 2 degrees HPT. Basal and nadir serum PTH levels were highly correlated: r = 0.95 and P < 0.05 in AD; r = 0.90 and P < 0.01 in 2 degrees HPT; r = 0.75 and P < 0.01 in NL. The slope of this relationship was less, however, both in AD and in 2 degrees HPT than in NL, P < 0.05 by analysis of co-variance. Thus, serum PTH levels fell below 20% of pre-infusion values in fewer subjects with AD (1 of 6) or 2 degrees HPT (9 of 31) than in NL (17 of 20) (chi 2 = 17.81, P < 0.005). The results indicate that the inhibitory effect of calcium on PTH release in vivo does not differ in AD and 2 degrees HPT despite marked differences in basal serum PTH levels. Variations in functional parathyroid gland mass rather than disturbances in calcium-sensing by the parathyroids probably account not only for the lower basal serum PTH levels in patients with AD compared to those with 2 degrees HPT, but also for the moderately elevated serum PTH values commonly seen in patients with AD.     

The basal concentration and characteristics of the diurnal secretory rate of prolactin in women with primary hypothyroidism]

Basal concentration was measured of prolactin (PRL) as were its diurnal fluctuations in blood depending on the clinical association of primary hypothyrosis (PH) with lactorrhea-amenorrhea, lactorrhea only or lactorrhea associated with disturbances in menstrual and reproductive functions that differ from those in amenorrhea, and without such disturbances. Patients with lactorrhea-amenorrhea syndrome present with continual hyperprolactinemia and no physiological diurnal rythm of PRL secretion. In patients presenting without amenorrhea, and basal hyperprolactinemia, lactorrhea and disordered menses result from transitory "night-time" hyperprolactinemia. PH patients who do not present with lactorrhea and disordered menstrual and reproductive function show physiological diurnal rythm of PRL secretion, with its parameters corresponding to those in healthy women. The development of hyperprolactinemia in PH is not age-related; neither is it associated with severity of hypothyrosis.     

Reduced dopaminergic inhibition of thyrotrophin release in states of physiological hyperprolactinaemia

We have tested the hypothesis that physiological puerperal hyperprolactinaemia may be secondary to reduced hypothalamic dopaminergic inhibition of prolactin (PRL) release. Nine post-partum females with physiological hyperprolactinaemia (aged 19-40 years; mean basal PRL +/- SE, 2099 +/- 257 mU/1, range 1002-3762 mU/1) were studied and results compared with fourteen normoprolactinaemic females (basal PRL less than 400 mU/1; aged 18-36 years). Puerperal hyperprolactinaemic females showed a reduced TSH response to dopamine (DA) receptor blockade with metoclopramide (10 mg i.v.) compared with normal females over a 60-min period following drug administration (total incremental TSH change, mean +/- SE, mU/1; 0.5 +/- 0.3 v. 3.1 +/- 1.0 P less than 0.005). This finding of reduced dopaminergic inhibition of TSH release in females with physiological puerperal hyperprolactinaemia supports the view that an overall reduction in hypothalamic dopaminergic tone may contribute towards hyperprolactinaemia in post-partum women.     

Regulation of branched-chain amino acid metabolism in the lactating rat

There is evidence that during lactation, uptake of the essential branched-chain amino acids (BCAA) by mammary glands exceeds their output in milk protein. In this study, we have measured the potential of lactating rats to catabolize BCAA. The activity, relative protein and specific mRNA levels of the first two enzymes in the BCAA catabolic pathway, branched-chain aminotransferase (BCAT) and branched-chain alpha-keto acid dehydrogenase (BCKD), were measured in mammary gland, liver and skeletal muscle obtained from rat dams at peak lactation (12 d), from rat dams 24 h after weaning at peak lactation and from age-matched virgin controls. Western analysis showed that the mitochondrial BCATm isoenzyme was found in mammary gland. Comparison of lactating and control rats revealed that tissue BCATm activity, protein and mRNA were at least 10-fold higher in mammary tissue during lactation. Values were 1.3- to 1. 9-fold higher after 24 h of weaning. In mammary gland of lactating rats, the BCKD complex was fully active. In virgin controls and weaning dams, only about 20% of the complex was in the active state. Hypertrophy of the liver and mammary gland during lactation resulted in a 73% increase in total oxidative capacity in lactating rats. The results are consistent with increased expression of the BCATm gene in the mammary gland during lactation, whereas oxidation appears to be regulated primarily by changes in activity state (phosphorylation state) of BCKD.     

Hypothalamic-pituitary-adrenal axis function in patients with active rheumatoid arthritis: a controlled study using insulin hypoglycemia stress test and prolactin stimulation

OBJECTIVE: To study the response of cortisol and of prolactin (PRL) to specific stimuli in rheumatoid arthritis (RA). METHODS: We measured the response of cortisol to insulin induced hypoglycemia and of PRL to thyrotropin releasing hormone (TRH) in 10 patients with active RA and in 10 paired control subjects. All were women with regular menstrual cycles. They had never received corticosteroids before the study. The PRL concentration was assessed by chemiluminescence immune assay and the cortisol concentration by radioimmunoassay. RESULTS: The basal serum levels of cortisol (14.47+/-2.5 microg/dl) and PRL (10.1+/-1.3 ng/ml) in the RA group were not significantly different from those of the control group (12.3+/-1.1 microg/dl and 13.7+/-2.4 ng/ml, respectively). The peak value of cortisol after hypoglycemia was comparable in both groups (25.5+/-2.4 microg/dl in RA vs. 26.0+/-1.5 ng/ml in controls). The integrated cortisol response to hypoglycemia expressed as area under the response curve (AUC) did not differ significantly in either group (1927+/-196 in RA vs. 1828+/-84 in controls). The interval-specific "delta" cortisol response was significantly higher for the 30 to 45 min interval in controls compared to patients with RA (9.8+/-0.9 microg/dl vs. 6.1+/-1.1 microg/dl; p = 0.02). The peak of PRL after TRH did not differ significantly in both groups (56.4+/-6.4 ng/ml in RA vs. 66.3+/-7.7 ng/ml in controls) and the AUC of PRL secretion after TRH was comparable in both groups (3245+/-321 vs. 4128+/-541). CONCLUSION: Our findings suggest that active RA is associated with subtle dysfunction of the hypothalamic-pituitary-adrenal glucocorticoid function and normal PRL secretion.     

Revision of the nomenclature for the Bacillus thuringiensis pesticidal crystal proteins

The aim of this prospective study was to evaluate the bone mineral density (BMD) at lumbar spine and femoral neck levels and biochemical parameters of bone turnover in 20 consecutive hyperprolactinemic males before and after an 18-month treatment with different dopamine agonists. Six patients received bromocriptine at a dose of 2.5-10 mg/day; 7 patients received quinagolide at a dose of 0.075-0.3 mg/day; 7 patients received cabergoline at a dose of 0.5-1.5 mg/week. BMD, serum PRL, testosterone, dihydrotestosterone, and osteocalcin (OC), and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured before and every 6 months during treatment. At study entry, BMD values were lower in patients than controls at both lumbar spine (0.82 +/- 0.03 vs. 1.18 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.85 +/- 0.02 vs. 0.92 +/- 0.02 g/cm2; P < 0.05) levels. Osteopenia or osteoporosis was diagnosed in 16 patients at the lumbar spine and in 6 of them at the femoral neck level. A significant inverse correlation was found between lumbar spine and femoral neck BMD values and both PRL levels and disease duration (P < 0.01). In the 20 patients, serum OC levels were significantly lower (2.1 +/- 0.1 vs. 9.3 +/- 2.4 microg/L; P < 0.01), whereas Ntx levels were significantly higher (157.8 +/- 1.1 vs. 96.4 +/- 7.4 nmol bone collagen equivalent/mmol creatinine; P < 0.001) than control values. A significant inverse correlation was found between serum PRL and OC (P < 0.01), but not Ntx, levels. After 18 months of treatment, serum PRL levels were suppressed, and gonadal function was restored in all 20 patients, as shown by the normalization of serum T (from 2.2 +/- 0.2 to 5.0 +/- 0.2 microg/L) and dihydrotestosterone (0.3 +/- 0.02 vs. 0.5 +/- 0.01 nmol/L) levels, without any significant difference among groups. A progressive significant increase in serum OC levels together with a significant decrease in Ntx levels were observed after 6, 12, and 18 months of treatment in the 3 groups of patients. A slight, although significant, increase in BMD values was recorded in all patients after 18 months of bromocriptine, quinagolide, and cabergoline treatment, serum OC levels were normalized after treatment, whereas neither urinary Ntx levels nor BMD values were normalized by 18 months of treatment with dopaminergic agents. In conclusion, treatment with bromocriptine, quinagolide, and cabergoline for 18 months, although successfull in suppressing serum PRL levels and restoring gonadal function, was unable to restore lumbar spine and femoral neck BMD and normalize Ntx levels. However, BMD was slightly increased during treatment, suggesting that additional bone loss was prevented after treatment of hyperprolactinemia.     

Suckling-induced inhibition of luteinizing hormone secretion and follicular development in the early postpartum sow

The endocrine basis of lactational anestrus, the causes of reproductive dysfunction after early weaning, and the relationships among LH, FSH, and prolactin (PRL) secretion and follicular development were evaluated in sows weaned 6 h after farrowing (zero-weaned, n = 8) and in normally lactating sows (n = 9). An irregular, high-frequency episodic-type pattern of LH secretion was present in the early postpartum period, irrespective of treatment, and in a proportion of sows this pattern was associated with a marked elevation of baseline LH concentrations. This pattern of LH secretion was maintained in the zero-weaned sows but LH secretion was inhibited in lactating sows, resulting in a difference (p < 0.05) in mean plasma LH between groups 72-78 h postpartum. There were no differences in FSH between groups in any period of sampling. Variable but elevated plasma PRL was observed in suckled sows but declined (p < 0.05) to basal levels within 12 h of zero-weaning. Follicular development measured at laparotomy or slaughter 96 h postpartum was greater (p < 0.05) in zero-weaned than in control sows. The development of lactational anestrus in the sow therefore requires suckling-induced inhibition of LH secretion by 78 h postpartum. This inhibition of LH release does not appear to be causally related to short-term changes in PRL secretion.