摘要:

Techniques are described for the solid-phase synthesis of the decapeptide luteinizing hormone releasing factor (LRF) and for the testing of its biological activity in vitro (dispersed cells of rat pituitary gland in monolayer cultures). The biological activity of several (LH)LRF analogues is reported. Two analogues of the hypothalamic Luteinizing hormone releasingthalamic modified factor at the histidine-2 position were tested for biological activity (secretion of luteinizing hormone) in cultures of dis- persed rat anterior pituitary cells. The analogue in which glycine was substituted for histidine at position-2 [Gly2] LRF behaves as a partial agonist releasing less than 50 % of the luteinizing hormone secreted at maximum concentrations of the releasing factor, while the analogue in which histidine at position-2 is deleted has no significant agonist activity at any of the doses tested. When added to the cultured cells at molar ratios 103 to 101 times that of the luteinizing hormone releasing factor, both analogues decrease the amount of luteinizing hormone secreted in response to the releasing factor.

ISSN:0378-7346    

DOI:10.1159/000301848

出版商:S. Karger AG    

年代:1971

数据来源: Karger

摘要:

The release of LH, FSH, and prolactin has been investigated in intact male rats, in estrogen-treated male rats, and in castrated male rats. The injection of 2 μl of 0.15 m NaCl into the third ventricle to cause ventricular expansion in castrated animals stimulated markedly the release of LH. FSH release was also stimulated but only slightly. Prolactin release was inhibited. Intact rats or estrogen-treated rats responded not at all or to a much lesser extent than did the castrated rats. Serotonin creatinine sulfate, given intraventricularly, stimulated the release of LH in intact rats but suppressed the release of LH in castrated rats that occurred following ventricular expansion in these animals. N-acetyl-serotonin generally had no effect on LH release in intact rats, but, in an occasional animal, this indole markedly stimulated the release of LH. In castrated animals, N-acetyl-serotonin and melatonin suppressed LH release. These indoles appeared to have little effect on FSH release in these experiments. Prolactin release was stimulated by N-acetyl-serotonin.

ISSN:0378-7346    

DOI:10.1159/000301849

出版商:S. Karger AG    

年代:1971

数据来源: Karger

摘要:

Some of the contradictory postulates regarding gonadotropin action in infancy were reexamined. For the deprivation of newborn animals of endogenous gonadotropins, antiserum neutralizing theese hormones was administered from birth on. Using this approach it was elucidated that, even during the first week of life, gonadotropins stimulate development of ovarian somatic elements and are indispensable for this process. In the absence of the stimulatory action of endogenous gonadotropins, the normal ovarian development taking place during the first and second week of life was markedly altered and retarded. This was mainly evident from the reduction in the number of follicles which developed, the change in the appearance and ultrastructure of granulosa cells, the deficiency of thecal and of vascular development. That the observed alterations were due specifically to gonadotropin deprivation was proven by the fact that these alterations were prevented by the administration of human gonadotropins to mice deprived of endogenous gonadotropins. Substitution with human gonadotropins permitted the elucidation of the respective role of follicle-stimulating hormone (FSH) and FSH plus luteinizing hormone (LH) in the development of the infantile ovary. This was achieved by the use of HMG and of a biologically ‘pure FSH’ which was obtained by the neutralization of the LH activity present in HMG. FSH was found to be primarily responsible for the stimulation of granulosa cell proliferation, organization and structure. FSH plus LH, in addition to the FSH effects, initiated secretory activity of granulosa cells, increase in intrafollicular spaces, antrum formation, enrichment and maintenance of the theca layer and development of the vascular system. At the age of 14 days, the administration of HMG to gonadotropin-deprived animals even enhanced some of the developmental phases beyond that observed in ovaries of control animals at the same age. Oocyte growth seems to be independent of gonadotropins since it was similar in all experimental groups. The functional integrity of the growing oocytes in gonadotropin-deprived animals could not be assessed in this study.

ISSN:0378-7346    

DOI:10.1159/000301850

出版商:S. Karger AG    

年代:1971

数据来源: Karger

摘要:

Immunologic techniques have proven to be useful tools in characterizing the action of pituitary protein hormones on the target organs. Specifically, an antibody to luteinizing hormone can prevent ovulation, delay implantation, or cause fetal resorption depending on the time of administration of the antiserum to female rats. The immunologic interference with ovarian function appears to be associated with the steroidogenesis process during early pregnancy, and with fetal placental function during mid pregnancy in the rat. Progesterone synthesis is diminished, probably by the prevention of luteinizing hormone from stimulating the Δ5β hydroxysteroid dehadrogenase within the interstitial tissue of the ovary. In later pregnancy, the antibody combines with specific cells within the placenta, thereby eliminating any placental influence on the ovarian steroidogenic process.

ISSN:0378-7346    

DOI:10.1159/000301851

出版商:S. Karger AG    

年代:1971

数据来源: Karger

摘要:

Antagonists of pituitary trophic hormones may act either by inhibiting the synthesis and release of the hormone, by interfering with the interaction of the trophic hormone with its target tissue, or by inhibiting the intracellular response of the target cell. Taking the adrenocorticotrophin (ACTH) – adrenal cortical cell system some inhibitors of the “trophic” and “acute steroidogenic” responses of the cortical cells to ACTH are described. Finally the problems associated with using inhibitors of specific intracellular functions in the whole animal are considered.

ISSN:0378-7346    

DOI:10.1159/000301852

出版商:S. Karger AG    

年代:1971

数据来源: Karger

摘要:

Part. I: Prostaglandin F2α (PGF2α) was shown to be ‘the’ luteolysin in the ewe on the following criteria: (1) Hysterectomy and/or separation of the uterine horn from the ovary bearing a corpus luteum led to prolongation of the oestrous cycle, (2) PGF2α shortened the cycle when administered in the midluteal phase, (3) PGF2α was identified in uterine venous blood, (4) a mechanism for the transfer of PGF2α from the uterine vein to the ovarian artery was shown to exist, (5) the quantitative aspects of the secretion transfer mechanism and luteolytic potency of PGF2α were adequate to account for the observed phenomena. Part II: These criteria were applied for evaluation of PGF2α as ‘the’ luteolysin in the following species: cattle, goat, horse, pig, guinea pig, rat, hamster, rabbit, monkey, human. On present knowledge, there appeared to be a variation between species from those in which PGF2α was probably concerned in luteolysis and those in which the evidence was against such a role. Part III: PGF2α was shown to be luteolytic when given by continuous infusion for 3–6 h into the lumen of the uterus in cattle as well as sheep. The minimum effective dose was of the order of 7 g/kg. The application of this finding to artificial insemination programmes was discussed.

ISSN:0378-7346    

DOI:10.1159/000301853

出版商:S. Karger AG    

年代:1971

数据来源: Karger

摘要:

A group of adult hypophysectomized patients (due to cromophobe adenoma) was studied at different periods of time after operation. All of them showed loss of libido and potentia, low levels of urinary FSH and LH and of testosterone glucoronide. Daily doses of corticoids and thyroid hormone were administered. Testis biopsies were taken before and after each one of the following courses of treatment. The 14 patients were divided into 5 different groups. Group I, comprising 3 patients, was treated first with HMG (Pergonal-500, 3 ampoules per week) combined with HCG (3,000 IU per week). After 16 weeks, HMG continued to be administered, but HCG was discontinued and replaced by testosterone propionate at different weekly doses in each patient (200, 100 or 50 mg) during another 16 weeks. The 3 patients of group II were first administered HMG (similar dose and period of time as above) and then with HMG combined with testosterone (200, 100 or 50 mg, respectively). The 3 patients of group III were first treated with HCG in similar dose and period of time as above, and then with HCG combined with testosterone in similar dose and period of time as above. The 3 patients of group IV were given testosterone alone in similar doses and period of time as above. Finally, the 2 patients of group V were used as controls and no gonadotropins or testosterone treatment were administered during the period of the research. The following was observed: (1) HMG combined with HCG induced restoration of full spermatogenesis, development of mature Leydig cells and regression of preexistent peritubular hyalinosis. HMG alone showed a partial recovery of Leydig cells and of spermatogenesis until spermatid stages. HCG induced development of germinal cells until middle meiosis process and complete development of Leydig cells. (2) When testosterone was added to HMG or to HCG, an inhibitory effect was noted as judged by the regression of spermatogenesis and Leydig cells development, which was accompanied by reappearance of peritubular hyalinosis. The intensity of this inhibitory effect was dose-dependent. When testosterone was given alone, an almost complete atrophy of seminiferous tubules and Leydig cells was present. (3) The probable mechanism of action of testosterone upon the endogenously circulating or exogenously administred gonadotropins is discussed.

ISSN:0378-7346    

DOI:10.1159/000301854

出版商:S. Karger AG    

年代:1971

数据来源: Karger

摘要:

The release of serotonin (5-HT) from nerve terminals located within the medio-basal hypothalamus has been shown to interfere with the secretion of pituitary gonadotropins. In particular, it inhibits the cyclic surge of LH resulting in ovulation, and it facilitates the suckling-induced rise in plasma prolactin levels in lactating rats. The level of activity of 5-HT neurons also seems to affect the uptake of -3Hestradiol by the hypothalamus. The importance of 5-HT in the neuroendocrine control of gonadotropic secretion is discussed in the light of these findings.

ISSN:0378-7346    

DOI:10.1159/000301855

出版商:S. Karger AG    

年代:1971

数据来源: Karger

摘要:

A gonadotropin-releasing factor could be extracted from human hypothalamic tissue. Follicle-stimulating hormone (FSH)- and luteinizing hormone (LH)-releasing activities were assayed according to Ramirez and McCann. FSH and LH were testet according to Steelman and Pohley or Parlow. A minimal FSH-releasing activity was caused by 0.01 μg human FSH-releasing factor. The optimal dose was achieved with 0.025 μg. An increase of the dose up to 0.3 μg did not result in a further FSH release. 0.01 μg of the synthetic LH-/FSH-releasing factor showed a significant FSH release. An increase of the dose did not result in an increased FSH release. In contrast, the LH release was dose-dependent. The course of FSH release after application of 0.1 μg human gonadotropin-releasing factor showed the maximum after 30 min and reached the normal level after 2 h. Injection of 0.01 μg synthetic LH-releasing factor produced a maximum after 10 min and a smaller maximum after 60 min. The course of LH release after injection of 0.2 μg human gonadotropin-releasing factor showed a peak maximum 30 min and a second maximum 120 min after application. The synthetic LH-releasing factor showed a peak maximum after 5 min, followed by declines and maximas between 30 and 45 min and 100–120 min. Human gonadotropin-releasing factor and synthetic LH-/FSH-releasing factor showed a different behaviour. Chemical differences may be responsible for these differences.

ISSN:0378-7346    

DOI:10.1159/000301856

出版商:S. Karger AG    

年代:1971

数据来源: Karger

ISSN:0378-7346    

DOI:10.1159/000301857

出版商:S. Karger AG    

年代:1971

数据来源: Karger