Influence of melatonin on the sleep-independent component of prolactin secretion.

Sleep has a stimulatory effect on prolactin secretion. Recent studies in the human suggest the hypothesis that prolactin has also an endogenous sleep-independent rhythm, which can be influenced by endogenous melatonin. To investigate this hypothesis, the prolactin response to nighttime exposure to bright light was studied in eight women in detail. Light exposure induces a decrease in nocturnal melatonin secretion. It was demonstrated that exposure to bright light for 2 h at night caused a decrease in prolactin secretion, which surpassed significantly the decline one would expect by sleep deprivation only (P less than 0.01). This was associated with a similar decline in melatonin secretion. Fall and rise of prolactin secretion under these conditions were always preceded by decrease and rise in melatonin levels in all eight women studied. Based on these observations, it is concluded that melatonin is associated with an endogenous circadian component of prolactin secretion. As specific melatonin receptors have been identified in the human nucleus suprachiasmaticus, which is the "master" circadian pacemaker, the observed phenomenon might be mediated through this structure. An alternative explanation of our findings could be based on the fact that melatonin influences dopamine metabolism, which in turn alters prolactin secretion. It can also not be ruled out that melatonin might act via the opioid system, which then could affect prolactin secretion. The total secretory activity for both hormones (area under the curve) did not change under experimental conditions, when compared to a control group. This suggests that acute light exposure and sleep deprivation influence the secretory process rather than the synthesis of these two hormones. This is in agreement with the observation that changes in natural light exposure throughout the year do alter the amplitude, but not the total amount of melatonin secreted. Further studies are needed to answer the question of melatonin storage definitively, as it is commonly believed that melatonin is immediately released after synthesis. It is concluded that melatonin through its external modulator light might entrain the circadian sleep-independent component of prolactin secretion and via its action on prolactin could modulate reproductive processes.

[Rational hormonal diagnosis of oligomenorrhea]. / Rationelle hormonale Diagnostik der Oligomenorrhö.

In a study, conducted by two clinics in Berlin and Hamburg, specializing in reproductive endocrinology, the anamnestic, clinical, and laboratory data of 170 oligomenorrheic patients (menstrual intervals between 35 and 90 days) were evaluated in order to determine the frequency of possible causes of oligomenorrhea. Pathological hormone levels were found in two thirds of all patients. The order of frequency of abnormal hormone levels was as follows: hyperandrogenemia (testosterone and/or DHEA-sulfate) in 41.8%, hyperprolactinemia in 25.9%, abnormal thyroid function (TSH and/or TRH-induced TSH) in 21.7%, and hypergonadotropic FSH levels in 3.5% of all patients. There was an overlap of between two or more pathological conditions in one third of all patients. This study confirms results of a previous study in amenorrheic patients (Moltz et al., 1987 - see reference list), documenting hyperandrogenemia as the most frequent abnormality found in this group, followed by hyperprolactinemia. As can be expected, the percentage of women with no discernible abnormality was higher in oligomenorrheic patients when compared with the amenorrheic group (32.3% vs 7.7%). Furthermore, overweight patients were overrepresented in the oligomenorrheic group, while underweight patients were seen more frequently in the amenorrheic group. In view of these results of our study we recommend a detailed diagnostic follow-up in all younger patients with ovarian disorders who need to preserve their reproductive potential. This follow-up should include hyperprolactinemia, hypo-/hyperthyroidism, hyperandrogenemic and hypoestrogenemic states and exclusion of primary ovarian failure. In contrast to recommendations of WHO, issued in 1976, such diagnostic work allows an etiology oriented therapy decision and a therapy risk assessment in subgroups of patients, such as hyperandrogenemic patients, who receive clomiphene or gonadotropin treatment. Furthermore, it permits prophylactic considerations, for prevention of hirsutism and polycystic ovarian disease, struma and osteoporosis prophylaxis.

[Rational hormonal diagnosis of secondary amenorrhea]. / Rationelle hormonale Diagnostik der sekundären Amenorrhö.

The usefulness of the guideline recommended in 1976 by the World Health Organization (WHO) for the differential diagnosis of ovarian sterility needs critical reevaluation, since it does not take into account new aspects such as the pulsatility of GnRH secretion, androgen excess, or thyroid disorders and other phenomena related to ovarian dysfunction. In order to demonstrate the relative frequency of such phenomena, the authors examined 183 women with secondary amenorrhea of more than three months' duration (mean +/- SD = 12.7 +/- 18.4 months). The endocrine status of these women was examined under standardized conditions in two clinical endocrinology units in the cities of Hamburg and Berlin. The percentages of abnormal hormonal data (greater than mean +/- SD + gray zone) were as follows: testosterone (T) 39.9%; DHEA sulfate (DS) 29.5%; prolactin (PRL) 18.0%; TSH 11.5%; FSH or LH 26.8%; estradiol (E2) 30.1%. Among 96 patients with increased T and/or DS (52.5% of all patients), 53 patients (55.2%) did not show any clinical signs of androgenization (hirsutism, acne). Retrospective evaluation of all data revealed that a stepwise diagnostic procedure would have resulted in the following cumulative percentages of hormonal abnormalities: (1) T = 39.9%; (2) +DS = 52.5%; (3) +PRL = 60.2%; (4) +LH/FSH = 82.0%; (5) +E2 = 91.2%; (6) +TSH = 92.3%. Only in 7.7% of all patients were all hormonal parameters within normal ranges. Individual case analysis showed that 52.5% of all patients had hyperandrogenemia, while 18% had hypothalamic amenorrhea without any other pathologic condition; 17.5% had hyperprolactinemia and 3.3% primary ovarian insufficiency. Another 4.9% had hypothyroidism only, while 1.1% had exclusively hyperthyroidism. Combined hormonal deviations were found in 24% of all patients. Considering the differential diagnosis of secondary amenorrhea from an economic point of view, one comes to the conclusion that direct and indirect expenditures are similar in magnitude, no matter whether one prefers a conventional stepwise procedure or a one-step hormonal analysis encompassing all potentially relevant hormones (DM 859.00 + 10 weeks waiting time vs. DM 827.50 + 1 week waiting time). Androgen excess is much more frequent than was believed; hirsutism and/or acne by no means necessarily occur in cases of androgen excess. Hyperprolactinemia is less frequent than hyperandrogenemia. Thyroid status should be evaluated in all women with functional amenorrhea. The stepwise diagnostic procedure as recommended by the WHO is time-consuming, complicated, and sometimes incomplete in the diagnostic work-up, with obvious potential disadvantages for therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Myocardial lactate dehydrogenase isoenzyme distribution in the normal heart.

The isoenzyme pattern of the lactate-dehydrogenase (LDH) in different parts of the heart was measured by micro-isoelectric focusing. Samples were taken from the right and left auricle, the outer, middle and inner layer of the myocardial wall of both ventricles and from the papillary muscle of the left ventricle. The results show that the activity of LDH total and the isoenzyme pattern are different in the various parts of the heart. In both auricles the isoenzymes LDH 3,4,5 were mostly found, whereas in the ventricles a significant increase of LDH 1,2 could be seen. Additionally, there was a shift in the isoenzyme pattern from the outside to the inner part of the myocardium wall with a significant increase of LDH1.

[Isoelectric focusing of complex protein mixtures in the nanogram range in microgels (author's transl)]. / Isoelektrische Fokussierung in Mikrogelen zur Fraktionierung komplexer Proteingemische im Nanogrammbereich

A method is described for isolectric focusing of complex protein mixtures in 2, 5 or 10 mul capillaries. For one separation only 15- 50 ng of a protein mixture is needed. Isoelectric focusing is finished after 10 min, staining takes 20 min and destaining approximately 30 min. Using defined mixtures of Servalyt from different pH ranges, isoelectric focusing can be adapted to the protein sample to be fractionated. Protein peaks separated by isoelectric focusing can be electrophoretically eluted and for further analysis refractionated directly in a microgradient gel. The resolution power of microisoelectric focusing is as good as that of the wellknown macroprocedure, as is demonstrated by isoelectric focusing of the water soluble proteins from cerebellum and heart, of rat and human serum and of a human oncocytoma of the thyroid gland.