Significant Increase In Serum Concentration Research Articles

Effects of androgen therapy on prostatic markers in hemodialyzed patients.

We have prospectively studied the evolution of serum levels of the prostatic-specific antigen and prostatic acid phosphatase in 14 male hemodialyzed patients, receiving a cycle of nandrolone decanoate (200 mg intramuscularly, once a week, for six months) as treatment for anemia. Androgen administration did not produce significant increases in serum concentrations of both tumor markers (basal: 0.9 +/- 0.5 and 0.7 +/- 0.3 ng/ml; at six months: 1.3 +/- 1.1 and 0.8 +/- 0.7 ng/ml respectively). Only one patient had a value of prostatic-specific antigen over the normal range: 4.2 ng/mol at the sixth month period, with a rapid decrease after the withdrawal of androgens. All the remaining values of both markers were within the normal range. In another six patients undergoing a prolonged treatment with androgens (between 9 to 24 months), the serum levels of prostatic-specific antigen and prostatic acid phosphatase were within the normal range in all of them. Nandrolone decanoate administration does not induce increases in prostate tumor markers when it is used as treatment for anemia in hemodialyzed patients.

Beta-Carotene, vitamin A, and lung cancer chemoprevention: results of an intermediate endpoint study

A randomized, placebo-controlled clinical trial of beta-carotene and retinol was conducted with 755 former asbestos workers as study subjects. The targeted endpoint for the intervention study was a reduction in the incidence and prevalence of sputum atypia. The dosage of 50 mg beta-carotene/d and 25,000 IU retinol/d on alternate days resulted significant increases in serum concentrations of both agents with no clinically significant toxicity. Skin yellowing was observed in approximately 35% of patients and may have contributed adversely to protocol adherence. Baseline analysis revealed that smoking and drinking were associated with lower concentrations of serum beta-carotene, even after dietary carotene intake was adjusted for (P < 0.0001). Baseline concentrations of retinol were apparently lowered by smoking (P < 0.002) and increased by drinking (P < 0.0001). Drinking and smoking also were significantly related to lower beta-carotene concentrations after supplementation (P < 0.001). No significant reduction in sputum atypia was observed after treatment.

Evidence that reduced lipoprotein lipase activity is not a primary pathogenetic factor for hypertriglyceridemia in renal failure

The aim of the study was to document postheparin plasma lipoprotein lipase (LPL) and hepatic lipase activities and relate these to serum lipid, lipoprotein and apolipoprotein concentrations in 85 patients with kidney function ranging from normal to dialysis dependency. Strict selection criteria were applied in order to exclude conditions other than renal failure which may influence lipid metabolism. Stress was laid on minimizing proteinuria and inflammatory activity. The changes in the lipoprotein pattern were numerically strikingly modest compared to those previously reported. This probably reflected the intention to elucidate the contribution of reduced renal function as such to the dyslipoproteinemia of renal failure, a condition often associated with confounding factors. Significant increases in serum concentrations of triglycerides and apolipoprotein CIII were already observed in moderate renal failure, whereas serum concentrations of high density lipoprotein cholesterol and plasma LPL activities were decreased only in severe renal failure. Plasma LPL activities were not significantly reduced in hemodialysis patients (probably due to anticoagulation with low molecular weight heparin), but serum concentrations of triglycerides and apolipoprotein CIII were significantly increased. A multiple regression analysis, taking glomerular filtration rate, LPL and apolipoprotein CIII into account, showed that both plasma LPL activity and serum apolipoprotein CIII concentration independently predicted serum triglyceride concentration. However, serum apolipoprotein CIII concentration was a much stronger predictor than plasma LPL activity. Thus, a decrease in LPL activity does not seem to be a prerequisite for the hypertriglyceridemia of uremia, but it probably accentuates this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of sex‐steroid hormones on the regulation of lymphocyte beta 2‐adrenoceptors during the menstrual cycle.

1. Up to 40% of female asthmatic subjects suffer a premenstrual deterioration in their condition which may be ameliorated by progesterone supplementation, although the mechanism responsible for this phenomenon is not understood. In vitro studies have shown that female sex-steroid hormones potentiate the bronchorelaxant effect of isoprenaline, whilst in vivo it has been shown that females exhibit greater sensitivity of systemic beta 2-adrenoceptor responses. 2. The aim of the present study was to determine whether cyclical alterations in beta 2-adrenoceptor expression, occurring under the influence of ovarian sex-steroid hormones, may offer an explanation for these findings. In vitro parameters of lymphocyte beta 2-adrenoceptor function were investigated in nine normal female subjects (aged 24 +/- 2 years) during the follicular (day 2-4) and luteal (day 21-23) phases of their menstrual cycle, and results were compared with those of nine age-matched healthy male controls studied at the same time intervals. 3. In female subjects there were significant increases in serum concentrations of oestradiol (3.3-fold) and progesterone (10.6-fold) between the follicular and luteal phases of the menstrual cycle, whereas no changes occurred in males. 4. In females during the luteal phase, the increase in sex-steroid hormones was mirrored by an increase in lymphocyte beta 2-adrenoceptor density (Bmax) and in maximal cyclic AMP response to isoprenaline (Emax), which were significantly higher than in male subjects. Mean differences (95% CI) between male and female subjects on visit 2 were 1.09 (0.49 to 1.69) fmol/10(6) cells (P = 0.001) for Bmax, and 3.42 (0.80 to 6.04) pmol/10(6) cells (P = 0.02) for Emax.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum amino acids, liver status, and antiepileptic drug therapy in epilepsy.

Serum amino acid (AA) profiles are altered in epilepsy. It is not clear whether this is due to the disease process itself or to other variables such as seizure type, seizure frequency, duration of illness, medication, or altered liver function. We investigated serum AA profiles and liver enzymes in 73 epileptic patients and 90 healthy subjects and evaluated the data by analysis of variance to discriminate between age, sex, seizure type, duration of illness, seizure frequency, antiepileptic drug (AED) and increased serum liver enzyme levels, and their putative interaction with the serum AA profile. There was no correlation between the changes in the AA profile and age, duration of illness, seizure frequency, and seizure type. Seventy-two percent of the AED-treated patients and 33% of the unmedicated patients showed an increase in one or several serum liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or gamma-glutamyl transferase (gamma-GT)]; particularly gamma-GT. We observed a significant increase in serum concentrations of glutamine and glycine and decreased levels of taurine, threonine, serine, valine, methionine, isoleucine, leucine, phenylalanine, histidine, tryptophan, and arginine in AED-treated patients but not in unmedicated patients. These results show that the changes in the serum AA profiles of epileptic patients treated with AEDs occur in patients with alteration of serum liver enzymes; whether this implies a causal relation is still uncertain.

Longitudinal study of serum thyroid hormone levels during normal pregnancy

We undertook a prospective longitudinal study of thyroid function in 60 normal pregnant women and measured serum concentrations of T 4, triiodothyronine (T 3), T-uptake, thyroxine binding globulin (TBG), free thyroxine index (FTI), free T 4, albumin and thyrotropin (TSH). From these data we established reference ranges for each of these analytes for each trimester and examined the interrelationships between laboratory measurements of thyroid function tests. We observed significant increases in serum concentrations of thyrotropin and decreases in free T 4, assays commonly used as first line investigations of thyroid activity during pregnancy. However, the 95th centile intervals for both analytes remained within the reference range for nonpregnant women.

Differential serum responses of tocopherols and tocotrienols during vitamin supplementation in hypercholesterolaemic individuals without change in coronary risk factors

The effects of tocotrienol-rich vitamin E from palm oil on serum vitamin E concentrations, serum lipids, plasma prostaglandins and platelet function (assessed by bleeding time and aggregation) were investigated in 44 subjects (23 males, 21 females) with hypercholesterolaemia. Following a 6-week run-in period, subjects were randomized for 20 weeks to receive either tocotrienol or placebo (superolein from palm oil), in increasing dosages. By the 4th week of supplementation, and at lowest dosages, there were significant increases in serum concentrations of total vitamin E, total tocopherol, and total tocotrienol in the active, but not placebo group, and these persisted in the highest dosage group for 16 weeks. At no stage during the study were there any significant changes in serum lipids (total cholesterol, HDL cholesterol, LDL cholesterol or triglycerides), or any changes in lipids predictable by serum vitamin E status itself, even when body composition was taken into account. There were also no changes in plasma prostaglandins or in platelet function. Evidence was obtained that the serum responses to ingested tocotrienols and tocopherols favoured tocopherol over tocotrienol, and alpha tocopherol over gamma tocopherol.

Influences of photoperiod on sexual behaviour, neuroendocrine steroid receptors and adenohypophysial hormone secretion and gene expression in female golden hamsters

Exposure to short daylengths arrests the oestrous cycle, provokes daily gonadotrophin surges and reduces the ability of exogenous oestradiol to trigger behavioural receptivity in golden hamsters. In order to examine neuroendocrine effects of photoperiod which might underlie these responses, ovariectomized hamsters were maintained under long or short photoperiods for 54 days before treatment with cholesterol or various doses of oestradiol-17 beta. Short days reduced the ability of low doses of oestrogen to prime hamsters for the induction of oestrus by progesterone. Upon repetition of oestrogen priming 2 weeks later, photoperiod was without significant influence on the concentrations of nuclear oestrogen receptors or cytosolic progestin receptors in a block of tissue containing the hypothalamus and preoptic area. Oestradiol treatment provoked significant increases in serum concentrations of LH and prolactin in the afternoon, but photoperiod did not alter the positive-feedback efficacy of this gonadal steroid hormone. Adenohypophysial LH-beta subunit and prolactin mRNAs were suppressed by short days in ovariectomized hamsters not treated with oestradiol. Oestradiol decreased expression of the LH-beta subunit gene in both stimulatory and inhibitory photoperiods, but increased prolactin mRNA abundance in both long and short days. Photoperiod therefore exerts pronounced steroid-independent effects on phasic LH and prolactin secretion, but regulation of adenohypophysial abundance of LH-beta subunit and prolactin mRNAs by oestradiol is not markedly influenced by daylength. Photoperiodic regulation of the priming effects of oestradiol on behavioural receptivity may result from modulation of events occurring subsequent to steroid-receptor interactions, or involve changes in receptor populations not detectable by the present methods.

An experimental model of chronic renal disease in dogs by infusion of microspheres into the renal arterial circulation

SUMMARY The feasibility of renal arterial infusion of nonbiodegradable microspheres as a model of chronic renal disease in dogs was evaluated. Resin-coated, styrene-divinyl benzene copolymer microspheres were infused into the kidneys of healthy adult Beagles by direct injections of both renal arteries in a single surgical procedure. Injections of 25-μm diameter microspheres had minimal effect on either the clinical status or serum values of the dogs. Histologic examination revealed the majority of the microspheres lodged within the capillary beds of the glomeruli, and little change to the kidneys. However, injections of 50-μm diameter microspheres caused significant increases in serum concentrations of urea nitrogen and creatinine. Histologically, the larger microspheres obstructed afferent arterioles and small arteries, which caused diffuse glomerular necrosis and nephron damage. With doses ranging from 1 to 3 million microspheres/dog, a correlation between the quantity of microspheres injected and severity of renal damage was observed. The optimal dose for producing a model of moderate renal disease was determined to be 1.8 million microspheres/dog (0.9 million microspheres/kidney). During long-term studies, microsphere-injected dogs fed a moderately restricted protein ration remained relatively azotemic, compared with control dogs on the identical ration. During the 5-month postsurgical period, the serum urea nitrogen concentration averaged 18.41 ± 1.59 mg/dl (mean ± SE) for the microsphere-injected dogs vs 9.31 ± 0.38 for the control dogs (P &lt; 0.001). Similarly, the mean serum creatinine value was significantly higher (P = 0.020) for the microsphere-injected dogs, compared with the controls (1.28 ± 0.12 mg/dl vs 0.94 ± 0.03). In addition, the difference in mean endogenous creatinine clearance rates was statistically significant (microsphere-injected 1.02 ± 0.05 ml/min/kg, vs control 1.53 ± 0.06, P &lt; 0.001).

Gene synthesis, E. coli expression and purification of the bovine growth hormone releasing factor analog, (Leu 27,Hse 45) bGRF

The DNA sequence coding for an analog of bovine growth hormone releasing factor (bGRF), having the methionine at position 27 substituted by leucine, was chemically synthesized with flanking methionine codons. Tandem ligations of this sequence allowed the monomer or fusion proteins of 2, 4, or 8 bGRF units to be expressed in E. coli from a pBR322-based vector. Although the monomer and dimer genes do not generate detectable products by SDS-PAGE, the fusion products of 4 and 8 bGRF accumulate as insoluble aggregates representing over 20% of the cellular protein; there appears to be decreased protease susceptibility as the fusion protein increases in size. The inclusion body material was solubilized in formic acid and octameric bGRF was treated with cyanogen bromide to release the monomer containing the natural amino-terminal tyrosine and an unnatural carboxy-terminal homoserine lactone. The reaction conditions represented a compromise between minimizing a formic acid-dependent modification of bGRF and achieving complete digestion. About 150 g of the bGRF analog were isolated at ≥99% purity using ion exchange and preparative reverse-phase chromatography. Intravenous injection of this peptide into steers stimulates somatotropin release as measured by significant increases in serum concentrations of the hormone.

Human Biologic Response Modification by Interferon in the Absence of Measurable Serum Concentrations: A Comparative Trial of Subcutaneous and Intravenous Interferon-beta serine

The effect on a range of biologic responses of interferon-beta serine (IFN-beta ser), administered by either the sc or the iv route, was examined in 16 patients. Despite the absence of IFN in the serum of 13 of 16 patients after sc administration, biologic changes associated with IFN administration occurred. Significant increases in peripheral mononuclear cell surface proteins were evident. Monocyte human leukocyte antigen-DR (HLA-DR) showed a 23% increase in mean fluorescent intensity (P = .04) and a 9% increase in percentage of positive cells (P = .02); lymphocyte OKT10 had an 11% increase in percentage of positive cells (P less than .0001) and a 26% increase in mean fluorescent intensity (P = .002). Natural killer cell activity against the Change target increased by 125% (P = .004). Intracellular activity of 2',5'-oligoadenylate synthetase increased 297% at 24 hours and 226% at 48 hours (P less than .0001). Significant increases in serum concentrations of beta 2 microglobulin (24% at 24 hr and 27% at 48 hr, P less than .0001) and neopterin (85%, P = .0001 and 165%, P = .00001) were observed. These alterations after sc administration were similar quantitatively to those resulting from the same dose of IFN-beta ser given iv. Thus, serum IFN concentrations did not have to be measurable for IFN-beta ser to exert biologic activity. The different effects of two dose levels, 45 X 10(6) IU and 180 X 10(6) IU, also were compared independent of route. The higher dose resulted in greater increases over baseline of 2',5'-oligoadenylate synthetase activity (344% vs. 145% at 24 hr; 231% vs. 83% at 48 hr) and serum neopterin concentrations (185% vs. 99% at 24 hr; 271% vs. 153% at 48 hr). For all the other parameters, there was no significant difference between the two doses.

The effect of intralipid ® on polymorphonuclear leucocytes

Total parenteral nutrition is associated with a relatively high frequency of infections. Infusion of intravenous fat emulsions have been demonstrated to cause impairment of some functions of the white cells. We evaluated the effect of intravenous infusion of at emulsions (Intralipid ® 20%) on the function of the polymorphonuclear leucocytes. Motility, phagocytic activity, fungicidic activity, oxygen consumption, superoxide generation, ATP-consumption during phagocytosis, and chemotaxis were used as parameters for leucocyte function. Opsonization time was used as parameter for serum dependent activity of the leucocytes. Twenty-four normal persons were at random allocated to two groups of 12 persons receiving either 400 ml 20% Intralipid or 400 ml isotonic saline. There was a significant increase in serum concentration of triglyceride in the group receiving Intralipid ®. The motility of the leucocytes was slightly improved in this group after discontinuation of the infusions, but this change was not significant (0.05<p<0.10). All other parameters were completely unaffected by both the Intralipid ® and the saline infusions. All p- values were above 0.20. The function of the polymorphonuclear leucocytes is the refore not impaired by intravenous fat infusions. Thus, other factors than impairment of neutrophil function, because of infusion of fat emulsions, must be sought to explain the high frequency of infections in patients receiving parenteral nutrition.

Unusually long inflation times during percutaneous transluminal coronary angioplasty

Unusually prolonged balloon inflations (PBI) during percutaneous transluminal coronary angioplasty (PTCA) have been utilized in 26 consecutive patients to establish adequate coronary perfusion after shorter inflation times resulted in severe residual stenosis (N = 15), early arterial closure (N = 5), or extensive dissection (N = 6). Inflations lasted 1.5 to 15 min and 23/27 stenoses were successfully dilated. The average reduction in stenosis was 67% (90%-33%). Chest pain occurred in 34% vs. 7% (P less than 0.01), and ST changes occurred during 66% vs. 57% (NS) of PBI vs. short inflations. Four patients required coronary artery bypass surgery in spite of PBI, but none suffered an infarction. Electrocardiograms were unchanged in 22 patients and showed nonspecific ST-T wave changes in four. Cardiac enzymes obtained in nine patients failed to reveal a significant increase in serum concentration. We conclude that PBI is well tolerated and can successfully dilate lesions not responding to short inflations.

A two-site monoclonal enzyme immunoassay for pregnancy-associated α2-glycoprotein

A two-site monoclonal enzyme immunoassay (MEIA) was developed for the determination of pregnancy-associated α 2-glycoprotein (PA α 2G) in serum. The minimum detectable level was 35 ng/ml. No immunochemical interaction with the closely related α 2-macroglobulin was found. Serum levels in 145 normal healthy males and non-pregnant females were 1.8 ± 2.8 μg/ml and 6.2 ± 3.5 μg/ml (mean ± SD), respectively, both significantly lower than previously reported. The distribution in the normal population was characteristically different when males and females were compared. No increase with age was found. During pregnancy, a significant increase in serum concentration was observed with average levels of 320 ± 200 μg/ml at term (mean ± SD), a 50-fold increase in concentration. As a tumor marker for breast and ovarian cancer, PA α 2G was found to be of no value. The present study emphasizes that a reevaluation of PA α 2G levels must be undertaken in order to assess the clinical and biological significance of this protein.

In-vivo evaluation of dopamine receptor-mediated inhibition of gonadotrophin secretion from the pituitary gland of the goldfish, Carassius auratus.

Dopamine acts directly on the pituitary to modulate gonadotrophin (GtH) secretion in goldfish (Carassius auratus). In the light of this important role for dopamine in the regulation of goldfish reproduction, this investigation was designed to evaluate the receptor specificity of this dopamine inhibition and to describe the use of domperidone, a specific dopamine D2-receptor antagonist, in the manipulation of pituitary function in goldfish. To investigate the specificity of dopamine inhibition of GtH secretion, selected dopamine receptor antagonists were injected i.p. to block dopamine receptors thereby increasing GtH secretion as reflected by increased serum concentrations of GtH. Serum GtH levels were significantly increased by the active stereoisomer (-)-sulpiride in a dose-related fashion; (+)-sulpiride had no effect. Comparison of dopamine antagonists at low doses indicated that only domperidone and pimozide caused significant increases in serum concentrations of GtH. Dopamine antagonists potentiated the action of a gonadotrophin-releasing hormone analogue (GnRH-A) with an order of potency of domperidone = pimozide greater than metoclopramide = fluphenazine. [3H]Domperidone, injected i.p. with unlabelled domperidone, entered the blood and achieved maximum concentrations 12 h after injection, but did not accumulate in the brain in appreciable amounts. Gonadal 3H radioactivity was usually equal to or in excess of blood radioactivity, while [3H]domperidone was highly concentrated in the pituitary in a time-dependent fashion, with maximal accumulation occurring 24 h after injection. The time-course of pituitary accumulation of [3H]domperidone correlated well with the temporal increase in serum GtH levels in response to i.p. injected domperidone or domperidone plus an analogue of LHRH. Domperidone increased serum concentrations of GtH in a dose-related fashion; an analogue of salmon GnRH (sGnRH-A) increased the sensitivity and magnitude of the serum GtH response to domperidone. Serum concentrations of GtH were increased by sGnRH-A in a dose-related fashion; a low dose of domperidone substantially increased the sensitivity of the serum GtH response to sGnRH-A. These results indicate that dopamine inhibits GtH secretion from the goldfish pituitary by acting through a specific mechanism mediated by a dopamine D2 receptor. Domperidone increased serum concentrations of GtH, potentiated the action of gonadotrophin-releasing hormones and did not pass into the brain after i.p. injection into goldfish. The data also suggest that dopamine and GnRH, although acting through different receptors, influence the effect of each other on GtH release.

A possible dual regulation of prolactin release by the serotoninergic system in rats at pro-oestrus and during late pregnancy: role of ovarian hormones.

The effect of para-chlorophenylalanine (pCPA), an inhibitor of serotonin synthesis, on prolactin release was studied in rats on the day of pro-oestrus and at the end of pregnancy (day 19). The surges of prolactin normally seen in the afternoon of pro-oestrus in intact rats and in rats ovariectomized on dioestrous day 2 and primed with oestrogen were significantly inhibited by pCPA treatment. Administration of 5-hydroxytryptophan reversed the inhibitory action of pCPA on prolactin release. Treatment with progesterone also completely reversed the inhibitory effect of pCPA on prolactin release in pro-oestrous rats and partially reversed it in ovariectomized oestrogen-treated rats. Ovariectomy on day 19 of pregnancy induced a significant release of prolactin 12 and 24 h later. Administration of pCPA on day 18 of pregnancy produced a marked increase in serum concentrations of prolactin on days 19 and 20 in rats left intact or ovariectomized on day 19. Administration of 5-hydroxytryptophan significantly reversed this stimulatory effect of pCPA on prolactin release but did not modify the release of prolactin induced by ovariectomy. Methiothepin (1-[10,11-dihydro-8-(methylthio) less than b,f greater than thiepin-10,41]-4-methylpiperazine maleate), a serotonin receptor blocker, also induced a significant increase in serum concentrations of prolactin on day 20 of pregnancy in rats left intact or ovariectomized on day 19. These results suggest the existence of different serotoninergic actions in the regulation of prolactin release at pro-oestrus and in late pregnancy. Serotonin facilitates the surges of serum prolactin released at pro-oestrus and in ovariectomized rats treated with oestrogen; progesterone enhances this effect.(ABSTRACT TRUNCATED AT 250 WORDS)

AMINO ACID SUPPLEMENTATION OF AMMONIATED MUSTARD MEAL FOR USE IN SWINE FEEDS

Ammoniated mustard meal (MM) was prepared in a pilot plant by expelling and hexane-extracting brown mustard seed (Brassica juncea (L.) Coss.) and applying steam, ammonia and water in the desolventizer. Barley-wheat (2:1)-based diets containing MM (16.8%) or MM + lysine (0.20%) or MM + lysine + isoleucine (0.1%) were compared to similar diets containing soybean meal (15.3%) or canola meal (21.6%). Each diet was fed to eight crossbred barows between 24 and 52 kg liveweight. Chemical scores indicated that the unsupplemented MM diet was first- and second-limiting in lysine and isoleucine, respectively. Compared to the unsupplemented MM diet, supplemental lysine significantly improved the feed:gain ratio (2.80 vs. 2.51) while adding both lysine and isoleucine improved daily gain (574 vs. 684 g/day). Lysine and isoleucine supplementation resulted in significant increases in serum concentrations of these amino acids, confirming observations made regarding gains and feed:gain ratio. The isoleucine deficiency associated with MM-supplemented diets may be nutritionally important only in the early part of the grower phase. However, lysine supplementation appears to be necessary throughout the grower period. Key words: Mustard meal, ammoniation, feeding trial, serum amino acids, lysine, isoleucine

Elevated serum parathyroid hormone, calcitonin, and 1,25-dihydroxyvitamin D in lactating women nursing twins

The roles of vitamin D, calcitonin, and parathyroid hormone in calcium metabolism during lactation may be more evident in women secreting very large amounts of milk for a number of months, as in mothers nursing twins. We report significant increases in serum concentrations of parathyroid hormone, calcitonin, and l,25(OH)2 vitamin D in mothers nursing twins compared to mothers nursing single infants. Serum concentrations of calcium actually increased in both groups during lactation. Maternal intakes of calories, calcium, and phosphorus were significantly higher in mothers nursing twins. Thus, mothers nursing twins were able to compensate for higher calcium losses in breast milk by increased dietary intakes of calcium as well as increased serum concentrations of parathyroid hormone, calcitonin, and 1,25(OH)2 vitamin D.

Relationship of changes in serum concentrations of prolactin and testosterone during dopaminergic modulation in males.

To evaluate the effect of PRL on the male pituitary-gonadal system, serum concentrations of PRL, testosterone, LH and FSH were determined in healthy young men daily before, during, and after 3-day oral administration of bromocriptine, metoclopramide or sulpiride. Bromocriptine (2.5 mg as a single dose) caused, concurrently with a marked suppression of serum PRL, a significant increase of serum testosterone and a transient decrease of serum LH. The changes of PRL and testosterone were negatively correlated. With metoclopramide (10 mg q.i.d.) serum PRL was increased and testosterone inversely decreased. There was no change in LH and FSH. Sulpiride (50 mg q.i.d.) evoked the elevation of serum PRL and LH, but no change in testosterone. A significant increase in serum concentration of testosterone was also observed in a patient with PRL-producing pituitary tumour and four out of seven patients with acromegaly during bromocriptine treatment. These results suggest an inhibitory effect of PRL on testosterone secretion at the gonadal level, or direct dopaminergic stimulatory control of testosterone secretion.

Can reduced consumption of gonadotrophins account for ovarian compensation in unilaterally ovariectomized, immature mice injected with gonadotrophins?

The effect of unilateral ovariectomy on ovulation rates in immature mice was studied. Ovulations were induced by injecting PMSG and hCG and their number was determined by counting tubal oocytes. A 2--3-fold increase in number of ovulations per ovary was observed after unilateral ovariectomy, and daily injections of progesterone abolished this ovulatory compensation. No significant increase in serum concentrations of immunoreactive FSH and LH was observed at 4, 8, 32 and 51 h after unilateral ovariectomy. Progesterone treatment lowered FSH levels at all times, while LH was unaffected. In intact mice, ovarian sensitivity to PMSG and hCG was not substantially affected by progesterone. Ovulatory compensation in immature gonadotrophin-injected mice appears to arise through a negative feedback mechanism and transiently increased secretion of pituitary gonadotrophin rather than through a greater utilization of a fixed amount of gonadotrophin.