The LH-releasing activity of GnRH and nine synthetic GnRH derivatives was tested in pituitary monolayer cell culture prepared from female rats. D-amino acid-substituted analogs were found to be 12 to 18-fold as active as GnRH, while D-amino acid GnRH-[1-9]-ethylamide analogs showed 15 to 38-fold activity as compared to GnRH. Dehydroproline-GnRH was equipotent with the parent compound. Asp(A)6-GnRH-EA was less active than GnRH and it was a partial agonist only. All peptides stimulated intracellular cAMP content of the cultured cells at 1 hr and 4 hr of incubation. A nearly uniform 1.8 to 2-fold increase above basal cAMP could be observed with all peptides tested at their maximally active concentrations. However, no correlation could be established between the relative LH-releasing activities and cAMP-elevating potencies of the peptides. The findings suggest that cAMP may not be involved in overall LH-release by GnRH but leave the possibility open that cAMP could be involved in certain steps of mobilizing compartmentalized LH pools of pituitary gonadotrophs.

Animals↗

PubMedDate not supplied

LH-RH antagonist inhibits gonadal steroid secretion in vitro.

This investigation was aimed at studying the direct action of LH-RH derivatives on gonadal function. Modulation by LH-RH antagonist (Ac-[D-beta-Nal1, D-p-Cl-Phe2, D-Trp3, D-Arg6, D-Ala10]-LH-RH) and agonist of LH-RH (D-Ser(TBU)6, AzaGly10-LH-RH) and native LH-RH of HCG-stimulated steroidogenesis in testicular Leydig cells and luteal cells was studied in vitro. The LH-RH antagonist (3.2 X 10(-8) M) was found to change ED50 of HCG from 2 X 10(-11) M to 5.5 X 10(-11) M in the Leydig cell culture system. In addition, the antagonist was noted to override the stimulatory action of native LH-RH in Leydig cells. Furthermore, the agonist was found to augment HCG-provoked testosterone secretion. Similarly, the LH-RH antagonist at 10(-9) M blunted HCG-stimulated progesterone secretion in the luteal cell culture system and increased the ED50 of HCG from 8.7 X 10(-13) to 7.7 X 10(-12) M. In contrast to the Leydig cell culture system native LH-RH (10(-8) M) and the agonist (10(-8) M) increased the ED50 of HCG in luteal cells from 8.7 X 10(-13) M to 3 X 10(-12) M and 2.3 X 10(-12) M, respectively. Present data combine to suggest that LH-RH antagonists act at least partially at the gonadal level and may be clinically useful to inhibit Leydig cell and ovarian function.

Animals↗

PubMedDate not supplied

HER-2 oncogene is not amplified in primary carcinoma of the fallopian tube. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

73 women suffering from primary carcinoma of the fallopian tube underwent surgical excision of their tubes. The tissue was embedded in paraffin and investigated for HER-2 oncogene amplification with a quantitative polymerase chain reaction method. DNA could be extracted and successfully prepared in 65/73 samples. None of the tissue samples exhibited amplified the HER-2 oncogene. Data suggest that the HER-2 oncogene does not play a role in tumor transformation and progression in fallopian tube carcinomas. This contrasts with observations in ovarian carcinomas, with which fallopian tube carcinomas share many clinical, histological and biochemical similarities.

Base Sequence↗

PubMedDate not supplied

[Endocrine changes following progesterone substitution in early pregnancy].

250 mg hydroxy-progesteronecaproate was used for intramuscular administration in 25 patients, between 11 and 15 week's gestation, presenting either with a history of recurrent abortion or being admitted because of threatened abortion. Beta-HCG and progesterone concentrations were determined twice at intervals of 24 hours. Three women aborted without showing any increase in Beta-HCG levels nore in progesterone levels. In 20 patients Beta-HCG concentrations increased significantly after the medication, whereas only 5 patients showed a rise in progesterone levels. In 14 patients serum progesterone concentrations decreased making the use of progestational steroids in the management of threatened abortion questionable.

17 alpha-Hydroxyprogesterone Caproate↗

PubMedDate not supplied

[13, 14-Dihydro-15-keto-PGF2 alpha (PGFM) and progesterone serum levels in labor].

Progesterone and PGFM serum levels were estimated by RIA in patients with spontaneous and induced labor. Induction of labor was performed by amniotomy or by local application of prostaglandins. Mean progesterone serum levels were at 130 ng/ml at the time of admission into the labor-room, and declined to mean levels of some 50 ng/ml in all 3 groups of patients 30 minutes after placenta expulsion. Mean PGFM serum levels were 2,5 to 3,5 times higher in patients with spontaneous labor than in those in whom labor was induced. Parallel decline of progesterone and PGFM serum levels was noted in patients with spontaneous labor, whereas declining progesterone levels but increasing PGFM serum levels were observed in patients with induced labor. These data combine to suggest that an increase in PGFM serum levels may be the cause for the onset of labor. But, the question whether progesterone triggers these processes cannot be answered by the present observations.

Dinoprost↗

PubMedDate not supplied

Detection of oestrogen and progesterone receptor expression in breast tumors by semiquantitative PCR.

BACKGROUND: Estimation of oestrogen receptors (ER) and progesterone receptors (PgR) by dextran-coated charcoal (DCC) or immunohistochemical methods have become standard practices in the management of breast cancer. MATERIALS AND METHODS: A "multiplex" polymerase chain reaction (PCR) system was developed for quantitative estimation of ER and PgR mRNA in breast tumour specimens. RESULTS: A statistically significant correlation could be found between the mRNA of the oestrogen and the progesterone receptor (p < or = 0.0001). Protein data defined in classes, compared with mRNA data showed a significant correlation for the oestrogen receptor (p < or = 0.0001) as well as for the progesterone receptor (p < or = 0.046). CONCLUSION: Messenger RNA could be determined by the present PCR system in tumours assayed as negative by DCC method. Therefore, this sensitive PCR procedure, which requires small amounts of material may be very useful as a diagnostic test to determine the choice of therapy.

Breast Neoplasms↗