[Effect of opioids and gamma-aminobutyric acid on ovulation]. / Uticaj opioida i gama-aminobuterne kiseline na ovulaciju.

UNLABELLED: Neurons secreting gonadotropin-releasing hormone (GnRH) contain receptors of gamma-aminobutyric acid (GABA), glutamate, fibroblast-growth factor, prolactin, beta-adrenergic receptor and dopamine receptor. Oestrogens and opioid peptides have a very important influence on gonadotropin secretion, but have no their own receptors in GnRH neurons. The role and interaction between gamma-aminobutyric acid and opioids in the inhibition of ovulation were studied, using valproate (GABA agonist) and naloxone (opioid antagonist) SUBJECT AND METHOD: Groups: postmenopausal women (50), postmenopausal women on oestrogen replacement therapy, consisting of 200 mcg/day transdermally oestrogen for one month (50), and women in luteal phase of their regular menstrual cycle (50). Thirty women from each group were studied after placebo (1st day) administration, and after 300, 600 or 1200 mg of valproate (2nd day). Gonadotropins and prolactin were measured in the same way, at intervals of 24 h, on the placebo day, and on the 2nd day. The interaction between naloxone and valproate was tested in 20 women from each group; day 1-placebo; day 2-naloxon (infusion-1.6 mg/h for 6 h); day 3-naloxon infusion, preceded by 1200 mg of valproate. RESULTS: Valproate. The concentration of luteinizing hormone (LH) was significantly decreased after the administration of valproate in postmenopausal women (up to 20%) and to women in luteal phase of the cycle (up to 80%). In substituted postmenopausal women there was no change in LH concentration after valproate administration. Naloxon. Naloxon infusion had no effect on LH concentration in postmenopausal women, and was significantly increased in mean serum LH in substituted postmenopausal women (52%) and in women in luteal phase of the cycle (27%). Valproate and naloxon. In women with a high oestrogen concentrations (substituted postmenopausal women) opioid blockade with naloxon (situation analogous to preovulatory phase of the cycle) contributed to the appearance of inhibitory influence of valproate on LH secretion (29.2 IU/L-after naloxone infusion; 13.2 IU/L-after administration of valproate and naloxone). In this group of patients there was no effect of valproate on LH previous secretion. CONCLUSION: GABA may have a significant role in the inhibition of ovulation because of its inhibitory role in LH secretion in the situations when oestrogen secretion is high, and opioid concentration is low.

[The polycystic ovary syndrome associated with ovarian tumor]. / Udruzenost sindroma policisticnih jajnika i tumora jajnika.

Case report of a girl with PCOD (polycystic ovarian disease) and Sertoli-Leydig ovarian tumour. A sixteen-year old girl was clinically, endocrinologically, echosonographically and laparoscopically examined, and polycystic ovarian disease was diagnosed. After a two-year period she was reexamined: normal adrenal function was confirmed and left ovarian tumour was discovered echosonographically. Therefore, she was operated on and adnexectomy of the left ovarian tumour and biopsy of the right ovary were done. The histopathologic analysis revealed the Sertoli-Leydig tumour of the left ovary and polycystic degeneration of the right ovary. In conclusion, because of the greater frequency of ovarian tumours in women with PCOD, the permanent follow-up of women with PCOD is necessary.

[Acute and chronic treatment with sodium valproate on gonadotropin hormone levels before menopause and during menopause]. / Akutno i hronicno lejstvo natrijum-valproata na nivo gonadotropnih hormona pre menopauze i u menopauzi.

INTRODUCTION: Gamma-aminobutyric acid receptors are found in neurons secreting gonadotropin-releasing hormone and in pituitary gonadotrophs. AIM OF THE STUDY: the examination of 1. acute and chronic effects of sodium-valproate (agonist of gamma-aminobutyric acid) on gonadotropin secretion in women; 2. the role of valproate in negative feed back effects of oestradiol; 3. if the effects of Valproate are hypothalamic or hypophyseal. PATIENTS AND METHOD: Three groups of patients are examined (50 patients in each group): 1. group of menopausal women; 2. group of substituted menopausal women (Estroderm TTS 200 g); 3. group of women in luteal phase. The same tests were performed in each group: a) examination of one dose acute effects of Valproate and dose dependent effects (doses of 300, 600, 1200 mg, given to three subgroups; there were ten women in each subgroup); b) examination of one dose acute effects of Valproate on pulsatile secretion of luteinizing hormone (from ten women of each group blood samples for determination of luteinizing hormone pulsatility were taken in 10-min-intervals over the period of 6 h, except in luteal phase, and over the period of 8 h; c) examination of chronic effects of Valproate (10 women of each group used 1200 mg of sodium valproate for one month, except women in luteal phase who were given Valproate for 10 days). RESULTS: Menopausal women. The maximal fall of luteinizing hormone was similar in all three doses: 14-20%; effects were dose dependent in this group of patients-the higher dose, the longer duration of effect. Substituted menopausal women. There was no effect on gonadotropin secretion. Women in luteal phase. The similar fall in luteinizing hormone and follicle stimulating hormone was recorded with 300 mg and 600 mg of Valproate. The maximal fall in luteinizing hormone was about 80% and of follicle stimulating hormone about 50%; effects were not dose dependent. In all three groups we found that (1) with suppression of the concentration of luteinizing hormone, the frequency of pulses of luteinizing hormone was changed; (2) chronic effects of Valproate on gonadotropin secretion were not significant; (3) prolactin values were not significantly affected by Valproate. DISCUSSION: The three groups have different values of reproductive hormones. It is not possible to determine endogenous gamma-aminobutyric level by using gamma-aminobutyric acid antagonists because of their convulsive actions. In a steroid deprived state (such as menopause women), Valproate causes the statistically significant fall in luteinizing hormone level (20% fall). This fall is present with every dose used in this study, and is dose dependent. The influence of Valproate on gonadotropin secretion is the most evident in luteal phase. This can be explained by permissive effects of progesterone on gamma-aminobutyric acid neurotransmission. According to these results, the effects of Valproate are dependent on ovarian steroid hormone levels. The change in luteinizing hormone pulse frequency after Valproate points to a hypothalamic site of action of Valproate. These results suggest that an acute increase in tone of gamma-aminobutyric acid may inhibit gonadotropin secretion in the oestrogen-deprived state, as well as during the luteal phase of the menstrual cycle. It is possible that neuron pathways using gamma-aminobutyric acid as a neurotransmitter interact with opioids in the inhibitory modulation of gonadotropins in human females.

[Sonographic monitoring of follicular maturation]. / Sonografsko pracenje folikularnog sazrevanja.

In recent years the interest for the evidence of ovulation and its follow-up has increased. This increase is especially evident in the field of out-body insemination. The ultrasound follow-up of ovulations is performed in the case of the growth of the follicle; determination of the ovulation ring; and observation of the Douglas free liquid. The authors present values of the follicular diameter on the 14th day of gestation in 34 patients with spontaneous, stimulated and induced cycles. In their opinion this procedure is a very useful method which, in addition to other parameters, enables a good inspection into the functioning of the ovary.

[The effect of hyperprolactinemia on the function of the hypothalamo-hypophyseal-ovarian axis]. / Uticaj hiperprolaktinemije na funkciju osovine hipotalamus-hipofiza-jajnici.

Seventy amenoroic, thirty oligomenoroic and twenty-four polymenoroic patients with hyperprolactinemia were observed. Anovulatory cycles: A statistically significant fall of the mean concentrations of gonadotropins and estradiol was not noted in any symptomatic group with the increase of the prolactin values. The mean values of gonadotrophins and estradiol were characteristic of hypogonadotropic hypogonadism when the concentration of prolactin was higher than 4000 mIU/l. The relations of gonadotrophins were changed and the value of FSH was significantly lower than LH when prolactin was up to 4000 mIU/l. The mean values of gonadotrophins did not differ significantly in amenoroic, oligomenoroic, and polymenoroic women belonging to the same group according to the prolactin concentrations. A significant difference however, was noted in the estradiol mean values. - Ovulatory cycles: Women belonging to the same group according to the prolactin concentrations did not differ significantly in the probability of ovulation, regardless of whether their cycle was amenoroic, oligomenoroic or polymenoroic. The probability of ovulation decreases significantly when prolactin values are higher than 2000 mIU/l.

Steroid receptors in human uterine carcinoma. Their biological importance and therapeutic implications.

Surgical material of primary uterine carcinoma from postmenopausal patients was analyzed with regard to cytosol content of estradiol (ER) and progesterone (PR) receptors, as well as their binding sites in nuclear compartment. A dextrancoated charcoal technique was used and binding data were calculated from Scatchard plots. In all examined specimens intracellular high-affinity, low-capacity estrogen - and progesterone-binding proteins (which have the characteristics of steroid receptors), with equilibrium dissociation constants (Kd's) of 10(-10)M and 10(-9)M respectively, have been observed in detectable levels. DNA binding ability of steroid-receptor complexes was examined and clearly demonstrated even at 4 degrees C by using DNA-cellulose slurry. Preheating of complexes at 25 degrees cause increased DNA binding ability in some specimens, but significant loss of this ability in other tumors. The relationship between the nuclear retention of steroid-receptor complexes and their interaction with nuclear components (giving a response) is discussed on the basis of steroid-responsive and unresponsive systems. Present investigation indicate that described steroid analysis may become an important tool in predicting the value of endocrine therapy in human uterine carcinoma.

[Changes in steroid receptors during histopathologic transformation of tissue in the human uterus]. / Promene steroidnih receptora u toku histopatoloske transformacije tkiva humanog uterusa.

Estrogen (ER) and progesterone receptors (PR) were analyzed in the cytosol and nuclei prepared from specimens of human uterine tissue of patients with certain disorders identified as hyperplasia endometrii adenomatosa, myoma uteri per magnum, adenocarcinoma endometrii and adenocarcinoma corporis uteri. These investigations have revealed a different level of ER and PR in analyzed tissue specimens, as well as the existence of a relationship between changes in receptor levels and respective Kd. These changes suggest a correlation between steroid receptor levels and the type of tissue transformation. The functionality of the receptors was analyzed by the ultracentrifugation of non-activated and activated steroid-receptor complexes in sucrose density gradients, as well as by the investigation of their interaction with isolated nuclei. These results indicate that some changes in steroid receptor molecules can be detected when the tissue turns from normal to malignant transformation. On the basis of this investigation it could be proposed that the analysis of activated and non-activated steroid-receptor complexes by means of the methods used in this study can be applied as a useful clinical tool in the determination of the endocrine dependence of transformed tissues, as well as for the optimum dosing of individual treatment of patients with uterine and other tissue carcinoma.

[Importance of determining gonadotropin levels in the serum in secondary amenorrhea]. / Znacaj odredivanja nivoa gonadotropina u serumu zena sa sekundarnom amenorejom.

On the basis of the results of the analysis of FSH, LH, and prolactin values in the serum of patients with secondary ammenorrhea, four groups of patients were formed: group 1 with low values of both gonadotropin hormones, group 2 with low FSH and high LH values, group 3 with high FSH and high LH values, and group 4 with the basdal gonadotropin values within normal. The use of functional tests proved helpful in the differentiation of the causes of amenorrhea. The use of the LH-RH test is of particular significance in the differentiation of the degree of changes in patients from group 1 and 4. To determine adequate therapy, the determination of estrogen in patients from group 1 and 3 is imperative. A successful treatment of secondary amenorrhea depends on its duration and a timely detection of its causes.