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The use of a synthetic peptide analog of LH-RH agonist--[D-Ala6, des Gly10, Pro9]-LH-RH ethylamide (surfagon) at microdoses and in short courses returned to normal the ovulatory cycle in the anovulatory condition in rats and caused luteinization of follicular cysts in rats and cows with further normalization of ovarian function. It is assumed that surfagon will be effective for the treatment of anovulatory condition and ovarian follicular cysts in women.

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The biological activity of surfagon (D-Ala6-desGly10-Pro9-ethylamide), a synthetic LH-RH agonist, is dozens of times higher than that of LH-RH in the test of rat hypophyseal stimulation of gonadotropin secretion in vivo and in vitro and in the ovulation induction test. A dose of surfagon required for the stimulation of LH secretion was considerably lower than that for the stimulation of FSH secretion. It may permit the use of surfagon in clinical practice for selective stimulation of secretion either of LH or total gonadotropins--LH and FSH.

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Interrelationship was studied between the influence of cysteamine on pain threshold and ulcerogenic effect on the duodenum. Cysteamine (350 mg/kg) induced analgesia in mice which was prevented by naloxone (1.5 mg/kg). In rats, cysteamine produced duodenal ulcers with concomitant analgesia. The intensity of ulceration was higher in animals with lower basal pain threshold. The correlation between central and peripheral effects of endogenous opioids in the development of experimental duodenal ulcers is discussed.

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Effect of melatonin on the gonadotropic activity of the hypothalamo-hypophysial system was investigated. The following proved to occur under the action of melatonin in sexually immature female rats: reduction of the spontaneous activity of luteinizing hormone (LH), of the LH content in the hypophysis, and of the endogenous luliberin stores in the arcuate nucleus; response of the hypophysis to the exogenous luliberin was also diminished. Single administration of low doses (from 1 to 100 micrograms) of melatonin was accompanied by reduction of cAMP content in the hypophysis and the hypothalamus. LH, luliberin and cAMP were determined by radiochemical methods. The results obtained indicated that the inhibitory influence of the pineal gland on the reproductive system was realized by melatonin, its hormone, through the hypothalamo-hypophysial complex.

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The changes in the luteinizing hormone (LH) level in the pineal gland were studied in rats depending on their sex and age, and under conditions of hypophysectomy or gonadectomy. In golden hamsters these changes were studied during the sexual cycle. The LH level was determined by the radioimmunological method. The gonadotropin content in animals aged under 15 days was independent of sex. At the age of 23 days the LH content was greater in the female animals than in the male, whereas in 30- and 60-day female rats it was decreased in comparison with that in the male animals. The LH concentration (per 1 mg of protein) was maximal in the pineal gland extracts of 5-day male and female rats. Gonadectomy of rats led to an approximately double elevation of the LH content in the pineal gland on the 13th postoperative day both in male and female rats. This index was restored to control values three weeks after the operation. From the onset to the termination of diestrus in hamsters the LH content in the pineal gland decreased from 215 to 75 pg/organ, and after diestrus followed by proestrus and estrus it rose to 180 pg/organ (P less than 0.05). A reduction of the LH content to the 10th postoperative day followed hypophysectomy in male and female pubertant rats; the gonadotropin content was restored in two weeks.

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The effect of pinealectomy on the luteinizing function of the hypophysis was studied in sexually mature rats. Following pinealectomy or sham operation rats were blinded in one experimental series, and both blinded and ovariectomized--in another series. Blood LH was determined radioimmunologically with hard-phase immunosorbent produced from antiserum. Pinealectomy does not alter the basic blood LH concentration in the blinded male and female animals. In comparison with the sham operated rats, LH mobilization from the hypophysis was elevated in the blinded ovariectomized rats with removed pineal gland under the action of the maximal LH-releasing hormone dose (200 ng per rat). In comparison with the initial, the hormone concentration increased in control group by 189%, and in the pinealectomized--by 301%. Pinealectomy intensified the autopotentiating action of the LH-releasing hormone (in repeated administration in 60 min) to 1119%, whereas in control rats an increase of the blood LH in response to the repeated adminstration of the LH-releasing hormone constituted 730% in comparison with the initial level. Pinealectomy decreased the inhibitory action of actidion on the autopotentiating effect of the LH-releasing hormone. Besides, pinealectomy accelerated the I125-LH elimination from the circulation in the blinded female rats = 7 min). It is supposed that LH biosynthesis was more active in the hypophysis of pinealectomized rats.

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Gonadotropin affiliated by biological and immunochemical properties to the luteinizing hormone of the hypophysis was revealed in the purified extracts from the bovine pineal glands. Biological properties of gonadotropin from the pineal glands were assessed by the reactions specific of the luteinizing hormone. Immunochemical properties of gonadotropin were studied by means of gel-precipitation in agar gel, immunoelectrophoresis and radioimmunochemical analysis. It was found that the specific content of gonadotropin in the epiphysis was 80 times lower than the specific content of the luteinizing hormone in the hypophysis, but exceeded the LH concentration in the blood serum 555 times and in the cerebrospinal fluid 6.8 times. Immunoreactive LH was absent in the extracts of the brain cortex, the liver and the ovaries. A theoretical interpretation of a possible physiological role of the LH-like gonadotropin in the endocrine regulation of the reproductive function of the organism is given in this work.

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