Synergistic effect of cortisol and thyrotrophin releasing hormone on lung maturation in the fetal sheep entails connective tissue maturation.

Pressure-volume relationships and collagen and elastin contents were measured in the lungs of fetal sheep infused either with saline (n = 4), thyrotrophin-releasing hormone (TRH; n = 6), cortisol (n = 9) or TRH plus cortisol (n = 10) at 128 days of gestation (term = 149 days) for 7 days. Lung distensibility (V40 = 1.8 +/- 0.1 ml/g wet wt; mean +/- SD) and stability (V5 = 0.6 +/- 0.1) increased along with collagen (C) (10.1 +/- 2.7 micrograms/mg) and elastin (E) contents (128 +/- 35 ng/mg) in the animals infused with TRH plus cortisol and were significantly higher (p < 0.05) than those observed in TRH (V40 0.62 +/- 0.07; V5 0.32 +/- 0.04; C 3.53 +/- 1.3; E 38.2 +/- 8.3), cortisol (V4 0.66 +/- 0.6; V5 0.27 +/- 0.03; C 4.27 +/- 0.8; E 41.02 +/- 12.7) or saline infused fetuses (V40 0.40 +/- 0.1; V5 0.20 +/- 0.06; C 3.28 +/- 0.9; E 31.5 +/- 9.2). Plasma concentrations of prolactin (PRL), triiodothyronine (T3) and cortisol (F) were also higher in the group of fetuses infused with both hormones in comparison with the other groups. In fetuses treated with TRH plus cortisol, PRL (32 +/- 8.3 ng/ml) and T3 (308.3 +/- 36 micrograms/dl) were significantly higher than in those infused with cortisol alone (PRL 3.7 +/- 2.3; T3 128 +/- 30) or with saline (PRL 4.2 +/- 1.6; T3 < 5 micrograms/dl). In the group treated with TRH alone, PRL also increased significantly (37 +/- 6.4), but T3 increased only slightly (18 +/- 3.4).(ABSTRACT TRUNCATED AT 250 WORDS)     

Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man

The aim of this study was to determine if a change in protein/carbohydrate ratio influences plasma steroid hormone concentrations. There is little information about the effects of specific dietary components on steroid hormone metabolism in humans. Testosterone concentrations in seven normal men were consistently higher after ten days on a high carbohydrate diet (468 +/- 34 ng/dl, mean +/- S.E.) than during a high protein diet (371 +/- 23 ng/dl, p less than 0.05) and were accompanied by parallel changes in sex hormone binding globulin (32.5 +/- 2.8 nmol/l vs. 23.4 +/- 1.6 nmol/l respectively, p less than 0.01). By contrast, cortisol concentrations were consistently lower during the high carbohydrate diet than during the high protein diet (7.74 +/- 0.71 micrograms/dl vs. 10.6 +/- 0.4 micrograms/dl respectively, p less than 0.05), and there were parallel changes in corticosteroid binding globulin concentrations (635 +/- 60 nmol/l vs. 754 +/- 31 nmol/l respectively, p less than 0.05). The diets were equal in total calories and fat. These consistent and reciprocal changes suggest that the ratio of protein to carbohydrate in the human diet is an important regulatory factor for steroid hormone plasma levels and for liver-derived hormone binding proteins.     

Acute starvation affects rat adrenal steroidogenesis

To determine how starvation affects adrenal steroidogenesis we measured the activities of 3 adrenal enzymes involved in corticosterone biosynthesis in a group of adult female rats. The animals were either starved for 7 days or fed ad libitum for the same period. Relative adrenal weight and plasma corticosterone levels were increased in the experimental group of animals compared to the control group (40 +/- 2 vs 27 +/- 1 mg/100 g body weight, P less than 0.001, and 45 +/- 4 vs 30 +/- 5 ng/dl, P less than 0.05 respectively). There were no differences in plasma ACTH levels between the groups (34 +/- 5 vs 26 +/- 4 pg/ml). 11-Hydroxylase activity was increased in the starved group of animals (18 +/- 3 vs 8 +/- 2 nmol/mg protein/min, P less than 0.01). 3 beta-Hydroxysteroid dehydrogenase and 21-hydroxylase activities were not different between the groups (19 +/- 2 vs 16 +/- 1 nmol/mg protein/min, and 100 +/- 10 vs 110 +/- 10 pmol/mg protein/min respectively). These results suggest that acute starvation in rats produces an increase in adrenal 11-hydroxylase activity.     

Thyroid hormones are required for daily rhythms of plasma corticosterone and prolactin concentration

Daily patterns of plasma corticosterone (B) and prolactin (PRL) concentration were measured in female rats which were intact (INTACT), thyroidectomized (THYREX), or thyroidectomized and given thyroxine (T₄) replacement (THYREX + T₄) (20 μg T₄/day). Bimodal daily rhythms of plasma B were present in INTACT rats and THYREX + T₄ rats. However, no plasma B rhythm was detectable in THYREX rats. THYREX + T₄ rats, which had greater mean T₄ concentrations than INTACT rats (6.0 μg/dl vs. 3.5 μg/dl), had a plasma B rhythm of greater amplitude than INTACT rats. Plasma PRL rhythms were detectable in INTACT and THYREX + T₄ rats, but not in THYREX rats. INTACT rats had a single peak in plasma PRL, whereas three plasma PRL peaks were present in THYREX + T₄ rats. It was concluded that thyroid hormones are required for the expression of plasma B and PRL rhythms and that the levels of thyroid hormones can alter the amplitude of the B rhythm and the shape of the PRL rhythm.     

Changes of beta-endorphin and somatostatin concentrations in different hypothalamic areas of female rats after chronic starvation

To study the effect of starvation on hypothalamic beta-endorphin and somatostatin (SRIF) concentrations in relation to starvation induced anestrus, groups of 8 rats were fed 50% of their normal daily chow consumption. Rats were sacrificed after 4, 8, 12, and 16 days during diestrus or anestrus. beta-endorphin concentrations decreased in the preoptic suprachiasmatic area (0.52 +/- 0.13 vs 0.21 +/- 0.05 ng/mg tissue wet weight) and increased in the posterior hypothalamus (0.31 +/- 0.06 vs 0.57 +/- 0.11 ng/mg) after 4 days of starvation. No significant change occurred in the arcuate nucleus or in the median eminence. On day 8 and 12 of starvation, beta-endorphin was unaltered in all areas compared to controls. Vaginal smears showed constant diestrus in a significant number of rats (5 out of 8) after 12 days. beta-endorphin concentrations in the arcuate nuclei of these rats were significantly reduced on day 16 (1.00 +/- 0.33 vs 0.30 +/- 0.11 ng/mg). The SRIF levels changed only in the median eminence with increased concentrations on day 12 (45.2 +/- 8.4 vs 79.5 +/- 14.8 ng/mg). At this time serum levels of luteinizing hormone (LH), prolactin (PRL), and growth hormone (GH) were significantly reduced. The results indicate that changes in hypothalamic beta-endorphin accompany the events leading to starvation induced anestrus.     

Involvement of peptide histidine isoleucine (PHI) in prolactin secretion induced by serotonin in rats

The possible role of hypothalamic peptide histidine isoleucine (PHI) in prolactin (PRL) secretion induced by serotoninergic mechanisms was investigated in male rats using a passive immunization technique. Intracerebroventricular injection of serotonin (5HT, 10 micrograms/rat) raised plasma PRL levels both in urethane-anesthetized rats and in conscious rats pretreated with normal rabbit serum (0.5 ml/rat, iv, 30 min before). Plasma PRL responses to 5HT were blunted in these animals when they were pretreated with rabbit antiserum specific for PHI (0.5 ml/rat, iv, 30 min before) (mean +/- SE peak plasma PRL: anesthetized rats 271.3 +/- 38.3 ng/ml vs 150.0 +/- 12.6 ng/ml, p less than 0.01, conscious rats 54.3 +/- 6.8 ng/ml vs 30.7 +/- 4.1 ng/ml, p less than 0.025). These results suggest that hypothalamic PHI is involved, at least in part, in PRL secretion induced by central serotoninergic stimulation in the rat.     

Indomethacin fails to alter basal or phenothiazine-induced prolactin concentrations in man.

In order to evaluate the possible role of prostaglandins in pituitary prolactin (PRL) secretion, PRL was serially measured following perphenazine (Trilafon) ingestion in 8 men before and after 5 days of indomethacin administration. Since estrogens have been shown to modulate prolactin secretion in man, serum steroids including estrone (E1), estradiol (E2), progesterone (P) and testosterone (T) were measured before and after indomethacin ingestion. Serum E1, P and T levels were similar during the pre- and post-indomethacin study periods: 56 +/- 4 (1 SEM) vs 48 +/- 5 pg/ml, 298 +/- 28 vs 315 +/- 32 pg/ml, and 8.1 +/- 0.7 vs 8.6 +/- 0.7 ng/ml, respectively. Serum E2 levels were slightly, but significantly, lower following indomethacin treatment at 30 +/- 3 vs 37 +/- 3 pg/ml (p less than .01). Basal serum PRL concentrations were unaffected by indomethacin administration (9 +/- 3 pre- vs 8 +/- 2 ng/ml post-drug treatment). Integrated perphenazine-induced PRL responses were likewise similar during the 2 study periods: 101 +/- 16 ng . hr/ml during the control period and 104 +/- 14 ng . hr/ml following indomethacin. Thus, short-term indomethacin treatment had no effect on basal or perphenazine-stimulated PRL secretion in men.     

The synchrony of prostaglandin-induced estrus in cows was reduced by pretreatment with hCG

The induction of optimal synchrony of estrus in cows requires synchronization of luteolysis and of the waves of follicular growth (follicular waves). The aim of this study was to determine whether hormonal treatments aimed at synchronizing follicular waves improved the synchrony of prostaglandin (PG)-induced estrus. In Experiment 1, cows were treated on Day 5 of the estrous cycle with saline in Group 1 (n = 25; 16 ml, i.v., 12 h apart), with hCG in Group 2 (n = 27; 3000 IU, i.v.), or with hCG and bovine follicular fluid (bFF) in Group 3 (n = 21; 16 ml, i.v., 12 h apart). On Day 12, all cows were treated with prostaglandin (PG; 500 micrograms cloprostenol, i.m.). In Experiment 2, cows were treated on Day 5 of the estrous cycle with saline (3 ml, i.m.) in Group 1 (n = 22) or with hCG (3000 IU, i.v.) in Group 2 (n = 20) and Group 3 (n = 22). On Day 12, the cows were treated with PG (500 micrograms in Groups 1 and 2; 1000 micrograms in Group 3). Blood samples for progesterone (P4) determination were collected on Day 12 (Experiment 1) or on Days 12 and 14 (Experiment 2). Cows were fitted with heat mount detectors and observed twice a day for signs of estrus. Four cows in Experiment 1 (1 cow each from Groups 1 and 2; 2 cows from Group 3) had plasma P4 concentrations below 1 ng/ml on Day 12 and were excluded from the analyses. In Experiment 1, cows treated with hCG or hCG + bFF had a more variable (P = 0.0007, P = 0.0005) day of occurrence of and a longer interval to estrus (5.9 +/- 0.7 d, P = 0.003 and 6.2 +/- 0.8 d, P = 0.005) than saline-treated cows (3.4 +/- 0.4 d). The plasma P4 concentrations on Day 12 were higher (P < 0.0001) in hCG- and in hCG + bFF-treated cows than in saline-treated cows (9.4 +/- 0.75 and 8.5 +/- 0.75 vs 4.1 +/- 0.27 ng/ml), but there was no correlation (P > 0.05) between plasma P4 concentrations and the interval to estrus. In Experiment 2, cows treated with hCG/500PG and hCG/1000PG had a more variable (P = 0.0007, P = 0.002) day of occurrence of and a longer interval to estrus (4.2 +/- 0.4 d, P = 0.04; 4.1 +/- 0.4 d, P = 0.03) than saline/500PG-treated cows (3.2 +/- 0.1 d). The concentrations of plasma P4 on Days 12 and 14 of both hCG/500PG- and hCG/1000PG-treated cows were higher (P < 0.05) than in saline/500PG-treated cows (7.3 +/- 0.64, 0.7 +/- 0.08 and 7.7 +/- 0.49, 0.7 +/- 0.06 vs 5.3 +/- 0.37, 0.5 +/- 0.03 ng/ml). The concentrations of plasma P4 on Days 12 or 14 and the interval to estrus were not correlated (P > 0.05) in any treatment group. The concentrations of plasma P4 on Days 12 and 14 of hCG/500PG- or hCG/1000PG-treated cows were correlated (r = 0.65, P < 0.05; r = 0.50, P < 0.05). This study indicated that treatment of cows with hCG on Day 5 of the estrous cycle reduced the synchrony of PG-induced estrus and that this reduction was not due to the failure of luteal regression.     

Plasma concentrations of pituitary hormones in 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated male rats

Experiments were conducted to test the hypothesis that acute TCDD toxicity is associated with pituitary hypofunction. Sexually mature male Sprague-Dawley rats were given graded doses of TCDD (0-100 micrograms/kg) and evaluated 7 days later. Despite pronounced hypophagia and body weight loss, plasma concentrations of growth hormone (GH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were not significantly affected by any dose of TCDD. Only prolactin (PRL) concentrations were reduced, while, as previously reported, thyroid-stimulating hormone concentrations were elevated. Also, plasma LH, PRL, and adrenocorticotropic hormone (ACTH) concentrations were not significantly affected 1, 2, 3, 4, 5, or 7 days after a single dose of TCDD (50 micrograms/kg). We conclude that (1) pituitary hypofunction is not a major cause of the initial stages of acute TCDD toxicity, (2) growth retardation in TCDD-treated rats is not the result of a deficiency of GH, (3) alterations in plasma corticosterone concentrations are due to altered responsiveness of the adrenal to ACTH stimulation rather than to changes in plasma ACTH concentrations, and (4) that impaired spermatogenesis is not associated with a decrease in plasma FSH concentrations. In addition, the lack of a consistent effect on plasma PRL concentrations suggests that alterations in plasma PRL concentrations do not play a critical role in the toxicity of TCDD. Finally, because TCDD treatment causes a serious androgenic deficiency without increasing the rates at which androgens are catabolized or excreted, the fact that plasma LH concentrations were unaffected indicates that TCDD treatment must reduce the responsiveness of the testis to LH stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

An acute increase in serum prolactin does not modify gonadotropin release in female rats

Attempts were made to find out whether hyperprolactinemia has an effect on the hypothalamo-pituitary response to estrogen feedback and LHRH stimulation. Adult female rats of Wistar strain were ovariectomized and received subcutaneous injection of 20 micrograms estradiol benzoate (EB) 3-4 weeks later (day-0). A second injection of 20 micrograms EB, when administered at noon on day-3, induced a highly significant increase in serum LH (p less than 0.001 vs. basal values), but not FSH, estimated at 1800 h on the same day. This EB-promoted LH release was not altered by pretreatment with rat PRL (5 micrograms/day), which was administered subcutaneously daily in the morning (1100 h) between day-1 and day-3. No statistical difference in the serum LH concentration was found when compared with the values for the control animals pretreated with 0.9% saline alone. Serum gonadotropins 15 min after LHRH administration (100 ng/100 g BW) in 32-day-old female rats were not statistically different between the animals pretreated with 5 micrograms PRL, which was given subcutaneously daily (at 0800 h) for 3 days, and the controls pretreated with 0.9% saline. These results suggest that an acute increase in serum PRL may not exert a negative effect on the gonadotropin release induced by estrogen feedback and LHRH stimulation.     

Inhibition by estrogen of autofeedback regulation of prolactin secretion

The effect of estradiol-17 beta (E2) on autofeedback regulation of prolactin (PRL) secretion was tested in ovariectomized rats after s.c. implantation of an (E2)-containing or empty silastic capsule, followed by i.v. injection of bovine PRL (b-PRL) or bovine serum albumin (BSA; 500 micrograms/100 g B.W.). Implantation of an E2 capsule (day 0), 2.5 mm or 5.0 mm in length, produced plasma E2 concentrations of 79 +/- 6 (9) and 140 +/- 8 pg/ml (8), respectively. Assay of PRL in plasma samples collected at 1 h intervals between 1100-1800 h on days 3, 4 and 5, after E2 capsule implantation showed a daily afternoon PRL surge. Empty capsule-treated rats did not show any afternoon PRL surge. Injection of b-PRL, but not BSA, at 1200 h on day 3 reduced basal PRL release both on days 3 and 4 in empty capsule-treated rats. In ovariectomized rats treated with a smaller E2 capsule (2.5 mm), b-PRL injection at 1200 h on day 3 reduced the amplitude of the afternoon surge of PRL and the total amount of PRL released on day 4. b-PRL, however, was ineffective in reducing PRL release in rats bearing the large E2 capsule (5.0 mm). These results suggest that high E2 levels in the blood can block the negative feedback action of PRL on PRL release.     

Evidence for direct inhibitory effects of dopamine on zona glomerulosa secretion of 18-hydroxycorticosterone in rhesus monkeys

This study was designed to more selectively investigate the dopaminergic regulation of 18-hydroxycorticosterone (18-OHB) and aldosterone production by the adrenal zona glomerulosa. Mature rhesus monkeys received either an infusion of dopamine (2 micrograms/kg/min) or 5% dextrose (0.2 ml/min) over a 60 min period (N=6). Dopamine had no effect on plasma levels of renin activity, cortisol, corticosterone, aldosterone or blood pressure. However, dopamine suppressed (p less than 0.05) plasma 18-OHB levels from a baseline of 31.6 +/- 3.5 ng/dl to 23.6 +/- 2.1 ng/dl at 60 min after onset of infusion. This observation is in agreement with some studies in humans but differs from others in which no depression in 18-OHB was observed following dopamine infusion. Dopamine infusion markedly (p less than 0.001) suppressed plasma PRL levels by 30 min after onset of infusion. Corticosteroid responses to metoclopramide (200 micrograms/kg) after dexamethasone 1 mg im every 6 h X 5 days or placebo treatment (vehicle im every 6 h X 5 days) was then evaluated. Dexamethasone significantly suppressed basal cortisol, corticosterone, 18-OHB and aldosterone. Although dexamethasone blunted the prolactin response, it did not inhibit the aldosterone response to metoclopramide. The 18-OHB response to metoclopramide was increased (p less than 0.01) following dexamethasone treatment. Following dexamethasone suppression, 18-OHB levels were still lowered (p less than 0.05) by dopamine infusion. These results suggest that dopamine selectively inhibits zona glomerulosa production of 18-OHB and aldosterone in rhesus monkeys.     

Death in ventricular fibrillation induced by isoproterenol in DOCA-salt pretreated rats preceded by changes in myocardial electrolytes

Serum and tissue content of sodium, potassium, magnesium and calcium was determined in controls and desoxycorticosterone acetate (DOCA)-salt treated rats to determine whether electrolyte changes preceded the development of isoproterenol-induced death in ventricular fibrillation. Control Sprague Dawley, male rats, were injected subcutaneously (s.c.) with either saline (Group A) or actinomycin D (0.1 mg/kg; Group B) once daily for 4 days. Other rats received 20 mg of DOCA by implantation, drank normal saline and were injected with either saline (Group C) or actinomycin D (Group D) once daily for 4 days. In the first part of the experiment, it was determined that none of 15 rats from Group C died when challenged with isoproterenol (150 micrograms/kg, s.c.) six days later: however, 13 out of 15 rats from Group D died within 29.1 +/- 15.0 minutes (mean +/- S.D.) from isoproterenol injection. Myocardial sodium was elevated (48.8 +/- 3.8 versus 36.3 +/- 1.9) and potassium decreased (60.4 +/- 3.4 versus 70.6 +/- 3.3, meq/kg wet weight, mean +/- S.D.) in rats that had succumbed to isoproterenol. In the second part of the experiment serum and tissues were removed from control and DOCA-saline pretreated rats before they died in ventricular fibrillation, 20 minutes after isoproterenol. DOCA-saline pretreated rats were hypernatremic and hypokalemic and exhibited higher sodium and lower potassium in skeletal muscle than control rats. Isoproterenol elicited hypokalemia in all rats, but it only elevated sodium and decreased potassium content in the myocardium of rats of Group D, that were more prone to die in ventricular fibrillation. It is concluded that myocardial electrolyte changes precede the onset of ventricular fibrillation and may be associated with the development of this dysrhythmia.     

Plasma progesterone and prolactin concentrations in overtly pseudopregnant bitches: a clinical study

Plasma concentrations of progesterone (P(4)) and prolactin (PRL) were measured in 35 bitches presented at veterinary clinics for symptoms of overt pseudopregnancy (PSP) between 50 and 95 days after the onset of proestrus. Results were compared to those from samples collected from 35 control bitches at comparable stages of the ovarian cycle (expressed as days after the onset of observed signs of proestrus). In the PSP bitches at 71.4+/-1.6 (mean+/-S.E.M.) days of the cycle, P(4) (1.5+/-0.2ng/mL) was lower (P<0.01) and PRL (16.0+/-1.9ng/mL) was higher (P<0.01), compared to P(4) (2.7+/-0.4ng/mL) and PRL (2.9+/-0.6ng/mL) in control bitches at 70.6+/-1.5 days of the cycle. Low P(4) was not a prerequisite for elevated PRL. Although elevated (> or =10ng/mL) PRL (20.9+/-2.0ng/mL) occurred more often with low (<2ng/mL) P(4) (20 of 24 cases) it also occurred with P(4) above 3ng/mL in two affected bitches and in two control bitches. Whether the occurrence of relatively low PRL concentrations (<4ng/mL) in samples obtained from 4 of the 35 pseudopregnant bitches reflected variable and often elevated PRL secretion or increased sensitivity to PRL in the absence of elevated prolactin in those animals was not determined. We inferred that elevated plasma PRL was often involved in the etiology of overt PSP; furthermore, a premature decline in circulating P(4) concentrations may be a factor in some instances.     

Effects of a fructose-enriched diet on plasma insulin and triglyceride concentration in SHR and WKY rats

Significant increases (P less than 0.001) in plasma insulin and triglyceride concentrations and in blood pressure were seen when SHR and WKY rats ate a fructose-enriched diet for 14 days. However, all of the changes were significantly accentuated (P less than 0.02-0.001) in SHR rats. Specifically the increment in plasma insulin concentration following the fructose-enriched diet was 42 +/- 4 microU/ml in SHR as compared to 25 +/- 4 microU/ml in WKY rats (P less than 0.001). Plasma triglyceride concentrations also increased to a greater degree in response to fructose in SHR rats (260 +/- 24 vs. 136 +/- 20 mg/dl, P less than 0.001). Finally, the fructose-induced increase in blood pressure of 29 +/- 4 mm of Hg in SHR rats was greater (P less than 0.02) than that seen in WKY rats (19 +/- 2 mm of Hg). There was no change in plasma glucose concentration in response to the fructose diet. WKY rats gained more weight than did the SHR rats. Thus, although plasma triglyceride and insulin concentration and blood pressure increased when either WKY or SHR rats consumed a fructose enriched diet, the magnitude of these changes was greater in SHR rats.     

Immunoreactive LHRH in chronic starved rats

The effects of chronic starvation (1/4 of ad libitum food intake) for 21 or 30 days were studied on the hypothalamic and serum concentrations of LHRH, the pituitary and serum concentrations of LH, and the weights of the anterior pituitary, ovary and uterus in adult female Wistar rats (chronic starved group, CSG). Control female rats were fed ad lib. for the same periods (control group, CG). On day 22 or 31, half of the rats of each group were weighed and sacrificed by decapitation. Since there were no difference on above parameters between the experiments on 22nd and 31st day, the results were combined for each parameters. At the time of sacrifice, the body weight of CSG was on the average 44% lower than that of CG rats, and also marked reduction in anterior pituitary (44%), ovarian (61%) and uterine weights (69%) was observed. Serum LH concentrations (mean +/- SE; 5.67 +/- 0.67 versus 33.30 +/- 6.00 ng/ml, P less than 0.001) and pituitary LH content (286.7 +/- 19.4 vs 451.0 +/- 32.8 micrograms, P less than 0.001) were significantly decreased in CSG than in CG rats. However, pituitary LH concentration was not reduced because of the proportional reduction to the pituitary weight of CSG rats. Hypothalamic immunoreactive LHRH (IR-LHRH) content in CSG showed a significant increase as compared to CG rats (5.77 +/- 0.52 vs 4.41 +/- 0.27 ng/hypothalamic extract, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Steroid and gonadotropin hormone levels in young African women with filarial infection

Serum levels of dehydroepiandrosterone sulfate (DHEAS), testosterone (T), progesterone (P), estradiol (E2), prolactin (PRL), cortisol (F) and gonadotropins (FSH, LH) were analysed by radioimmunoassay for 125 schoolgirls aged 14-16, in a zone of endemic filariasis 3 days after menses. Two groups were identified: the infected group in which 38 subjects had circulating Loa loa and or Mansonella perstans microfilariae as determined by the Knott's concentration technique, and the non-infected group (87 subjects without microfilaremia). All results are expressed as the mean +/- SD. No significant difference was found between the two groups for age (14.47 +/- 1.37 yr vs 14.50 +/- 1.37 yr) or for body wt (46.10 +/- 8.45 kg vs 47.06 +/- 8.26 kg). There was a tendency to lower levels of DHEAS in the infected group by comparison with controls (54.92 +/- 37.34 micrograms/dl vs 66.80 +/- 47.18 micrograms/dl) while in the same infected group more subjects had higher levels of prolactin by comparison with the control group (10.85 +/- 14.16 ng/ml vs 9.80 +/- 5.56 ng/ml). Testosterone, progesterone, estradiol levels and the LH/FSH ratio were lower in the infected group than in the non-infected group (P: 0.25 +/- 0.12 ng/ml vs 0.33 +/- 0.20 ng/ml, P less than 0.025; T: 0.55 +/- 0.17 ng/ml vs 0.62 +/- 0.19 ng/ml, P less than 0.05; E2: 32.95 +/- 19.63 pg/ml vs 66.98 +/- 54.83 pg/ml, P less than 0.001; LH/FSH: 0.91 +/- 0.44 vs 1.30 +/- 0.84, P less than 0.005) respectively. No significant difference was found between the two groups for F; however FSH levels correlated negatively with F levels only in the microfilaremia group (r = -0.38, n = 38, P less than 0.05). Our results suggest that the presence of microfilaremia in our subjects may have contributed to reduced steroid levels, perhaps by involvement of the cyclic AMP kinase system. These observations may explain the delayed menarche and androgen secretion found during puberty in a similar population living in the same zone of endemic filariasis. Microfilaremia should therefore be considered an environmental factor which mediates endocrine disorders in subjects living in tropical filariasis areas.     

Study of the change of prolactin and progesterone during dopaminergic agonist treatments in pseudopregnant bitches

In order to clarify the role of prolactin (PRL) and progesterone (P(4)) in the pathophysiology of canine pseudopregnancy (PSP) we designed an experiment, where we induced an abrupt pharmacological blockade of PRL secretion with dopaminergic agonists (DA) or placebo (PL). Thirty overtly pseudopregnant (PSPT) bitches were randomly allocated to three groups of 10 animals each: PL, bromocriptine (BR), and cabergoline (CA), which were treated with PL, 7.5microg/kg BR and 5microg/kg CA, respectively. On days 1, 7 and 14 (day 0: beginning of the treatment) all the animals were classified into grades of intensity of PSP clinical signs, considering serum or milk secretion and enlargement of the mammary glands. Presence or absence of treatment side effects were recorded and blood samples for PRL and P(4) determinations collected. Serum PRL and P(4) concentrations (ng/ml) of all the animals on day 1 were (least squares means [LSM]+/-S.E.M.) 17.70+/-2.05 and 1.13+/-0.13, respectively. During the experiment, serum PRL and P(4) concentrations decreased (day effect, P<0.05). During the experiment, serum PRL concentrations were lower in the DA treated group (BR and CA) compared with PL group (P<0.05). After a week of treatment, the percentage change of PRL was -62.52 versus 102.16+/-46.20 (P<0.01) for the treated (BR and CA) and PL groups, respectively. Conversely, no significant differences were found in the percent change in PRL between the BR and the CA groups nor in P(4) percentage change among all groups for the same week. Significant differences in the achievement of complete remission between treated and PL groups were found on days 7 (40 versus 0%, P<0.05) and 14 (90 versus 0%, P<0.01). No significant correlation between PRL and P(4) was found on day 1 in any of the animals. However, a significant correlation for the same hormones was found on days 7 and 14 for the DA treated groups (r=0.46, P<0.01). While in the PL group, PRL concentrations and intensity of clinical signs were not significantly correlated on days 1, 7 and 14; in the DA treated groups they were significantly correlated on days 7 and 14 (r=0.34, P<0.05). The presence of a positive correlation between PRL concentrations and the grades of intensity of clinical signs in the treated animals indicates the major role of PRL in PSP physiopathology. However, the lack of correlation during spontaneous involution of PSP in the PL group demonstrates that PRL concentrations do not completely explain the problem. In summary, abrupt changes in serum PRL seemed to be more important in ceasing PSP signs than total PRL concentrations in these groups of animals.     

Role of vasoactive intestinal polypeptide (VIP) in regulating the pituitary function in man

Intramuscular injection of synthetic VIP (200 micrograms) resulted in a rapid increase in plasma prolactin (PRL) concentrations in normal women, which was accompanied by the 4- to 7-fold increase in plasma VIP levels. Mean (+/- SE) peak values of plasma PRL obtained 15 min after the injection of VIP were higher than those of saline control (28.1 +/- 6.7 ng/ml vs. 11.4 +/- 1.6 ng/ml, p less than 0.05). Plasma growth hormone (GH) and cortisol levels were not affected by VIP in normal subjects. VIP injection raised plasma PRL levels (greater than 120% of the basal value) in all of 5 patients with prolactinoma. In 3 of 8 acromegalic patients, plasma GH was increased (greater than 150% of the basal value) by VIP injection. In the in vitro experiments, VIP (10(-8), 10(-7) and 10(-6) M) stimulated PRL release in a dose-related manner from the superfused pituitary adenoma cells obtained from two patients with prolactinoma. VIP-induced GH release from the superfused pituitary adenoma cells was also shown in 5 out of 6 acromegalic patients. VIP concentrations in the CSF were increased in most patients with hyperprolactinemia and a few cases with acromegaly. These findings indicate that VIP may play a role in regulating PRL secretion in man and may affect GH secretion from pituitary adenoma in acromegaly.     

Galactorrhea in subclinical hypothyroidism

Galactorrhea was found in 5 patients with subclinical hypothyroidism. The galactorrhea consisted of the discharge of a few drops of milk only under pressure. Serum T4 was in the lower level of the normal range, but serum T3 was normal (T4: 6.3 +/- 1.2 micrograms/dl, T3: 113 +/- 7 ng/dl). Basal serum TSH and PRL were slightly increased only in 2 and 1 cases, respectively. The PRL responses to TRH stimulation were exaggerated in all cases, although the basal levels were normal. An enlarged pituitary gland was observed in 1 patient by means of CT scanning. All patients were treated by T4 replacement. In serial TRH tests during the T4 replacement therapy, the PRL response was still increased even when the TSH response was normalized. Galactorrhea disappeared when the patients were treated with an increased dose of T4 (150-200 micrograms/day). Recurrence of galactorrhea was not observed even though replacement dose of T4 was later decreased to 100 micrograms/day in 4 cases. In patients with galactorrhea of unknown origin, subclinical hypothyroidism should not be ruled out even when their serum T4, T3, TSH and PRL are in the normal range. The TRH stimulation test is necessary to detect an exaggerated PRL response, as the cause of the galactorrhea. To differentiate this from pituitary microadenoma, observation of the effects of T4 replacement therapy on galactorrhea is essential.