PubMed Health⌕ Search

Biomedical subjects

A Gompel

Publications and source records attributed to A Gompel.

At least 55 records · Page 3Linked to original sources
PubMed1988

Induction of ovulation with pulsatile GnRH in hypothalamic amenorrhoea.

Pulsatile administration of gonadotrophin releasing hormone (GnRH) is a very effective treatment for induction of ovulation in hypothalamic amenorrhoea (HA). Thirty-seven women have been treated for a total of 117 cycles which resulted in 42 pregnancies--four treatment failures occurred. If these cycles are excluded, the 42 pregnancies were obtained within 2.3 cycles. One twin pregnancy occurred and no hyperstimulation was observed. The treatment was administered intravenously with a dosage schedule based on the grading of HA. We concluded that pulsatile GnRH was safe and very successful in induction of pregnancy in HA. Other indications (polycystic ovary syndrome and luteal phase defect) remain much less suitable for this treatment.

Amenorrhea↗
PubMed1988

[Pulsatile administration of GnRH: from the future to the present].

Since the first clinical reports of the successful induction of ovulations and pregnancies using pulsatile administration of the neuropeptide GnRH by G. Leyendecker and L. Wildt's group in 1979, the role of the hypothalamic generator, as demonstrated in primates by E. Knobil, is widely accepted in human reproduction. During this time, an increasing number of group has experienced these therapies and there continues to be some controversies about the route of administration, the indications, the need for adjuvant therapies. A correct evaluation of these therapies needs multicentric studies and more accurate criteria: the MINITEL network provides a fast, inexpensive way to collect data from different groups and to perform studies with larger sample sizes. The Life table analysis method represents the more suitable method for evaluating and for comparing various therapy regimens. LH plasma pulsatility studies have been performed in humans in order to classify various "supra-pituitary" reproductive disorders. These studies are exposed to several methodological drawbacks and must be cautiously interpreted. Modelling is one of the new methodological issues which can give access to more physiological parameters.

Female↗
PubMed1987

Antiestrogen action of progesterone in breast tissue.

This review analyzes recent data from international literature concerning the antiestrogen action of progesterone and progestins at the level of mammary cells in culture from either breast cancer lines or normal breast obtained from reduction mammoplasties. Most data indicate that progesterone and progestins have a strong antiestrogen effect on breast cell appreciated by the decrease of estradiol receptor content, the decrease of cell multiplication and the stimulation of 17 beta-hydroxysteroid activity which may be considered as a marker of breast cell differentiation dependent of progesterone receptor.

Animals↗
PubMed1987

[Antiestrogen action of progesterone in the breast].

This review analyzes recent data from international literature concerning the antiestrogen action of progesterone, progestins and the antiprogesterone RU 486 at the level of mammary cells in culture from either breast cancer lines or normal breast obtained from reduction mammoplasties. Most data indicate that progesterone, progestins and even RU 486 have a strong antiestrogen effect on breast cell appreciated by the decrease of estradiol receptor content, the decrease of cell multiplication and the stimulation of 17 beta-hydroxysteroid activity which may be considered as a marker of breast cell differentiation dependent of progesterone receptor.

Animals↗
PubMed1986

Antiestrogen action of progesterone in breast tissue.

In normal breast, estrogen stimulates growth of the ductal system, while lobular development depends on progesterone. Thus, estrogen and progesterone, when secreted in an adequate balance, permit the complete and proper development of the mammary gland. Progesterone may also have an antagonistic activity against estradiol, mediated through a decrease in the replenishment of the estrogen receptor, and also through increased 17 beta-hydroxysteroid dehydrogenase which leads to accelerated metabolism of estradiol to estrone in the target organ. Thus, it can be inferred that long periods of luteal phase defect leading to an unopposed estrogen effect on the breast might promote breast carcinogenesis.

17-Hydroxysteroid Dehydrogenases↗
PubMed1986

Effects of estradiol and promegestone on human breast cell cultures. An ultrastructural study.

Effects of estradiol (E2) and promegestone (R 5020) were tested on primary cultures of epithelial human breast cells prepared from surgical specimens of reduction mammoplasty. Comparative morphological studies were performed by means of transmission and scanning electron microscopy in cells without any hormonal adjunction and in those previously treated with E2 or E2 + R 5020. The results were as follows: In basal medium used as control the majority of epithelial cells, although well-differentiated, remained flat with few microvilli, well-developed Golgi apparatus and rough endoplasmic reticulum, was obvious. R 5020 added with E2 increased differentiation of epithelial cells covered with scarce long and branched microvilli, but reduced the turn-over of young cells. E2 seemed to generate more active proliferation of cells. R 5020 inhibited this effect and induced a higher differentiation of mammary epithelial cells.

Breast↗
PubMed1986

Estradiol/progesterone interaction in normal and pathologic breast cells.

In most target cells of the female genital tract, adequate cell differentiation is obtained via the successive and synergistic actions of estradiol (E2) and progesterone (P). This mainly due to the fact that progesterone receptor (PR) synthesis involves the prior action of estradiol through its receptor (ER). In normal breast, E2 stimulates the growth of the ductal system whereas lobular development depends on progesterone secretion. In other words E2 + P, when secreted in an adequate balance, permit the complete and proper development of the mammary gland. On the other hand progesterone may also have an antagonistic action against E2. The antiestrogen activity of progesterone is mediated through a decrease in the replenishment of E2 receptor and the synthesis of 17 beta-hydroxysteroid dehydrogenase, which leads to an accelerated metabolism of E2 to E1 in the target organ itself. These biochemical events, which have been well documented in the endometrium, have also been shown in cultures of normal breast epithelial cells as well as in differentiated fibroadenomas with high cellular density. In addition, data from the literature show that E2 added to human breast cells increases cell multiplication by means, eventually, of the synthesis of growth factors. Progesterone and progestins have a reverse effect. Data from our laboratory indicate that in normal cultured cells E2 and progestins are also antagonists with regard to cell multiplication. From these different data, it is postulated that in human beings, long periods of a luteal-phase defect leading to an unopposed estrogen effect might be a promoter of carcinogenesis in the breast.

17-Hydroxysteroid Dehydrogenases↗
PubMed1986

Contribution of plasma androstenedione to 5 alpha-androstanediol glucuronide in women with idiopathic hirsutism.

To confirm that plasma delta 4 androstenedione (delta 4) is the main precursor for 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (Adiol G) in patients with idiopathic hirsutism (IH), delta 4 was cutaneously applied to five normal women and five women with IH. Several parameters of androgen metabolism were assayed basally and throughout the studies. Those included plasma delta 4, testosterone, and dihydrotestosterone as well as urinary Adiol G and testosterone glucuronide excretion. Under basal conditions plasma testosterone, delta 4, and dihydrotestosterone did not differ significantly between the two groups of subjects. Urinary Adiol G excretion was significantly higher (P less than 0.01) in IH patients [123 +/- 36 (SE) micrograms/24 h] than in the normal women group (45 +/- 20 micrograms/24 h). After percutaneous administration of delta 4, plasma delta 4 increased in both groups by nearly 600% and there was a 300% increase in Adiol G excretion in IH patients (336 +/- 57 micrograms/24 h), whereas only a 50% increase occurred in normal women (65 +/- 17 micrograms/24 h). We postulate that plasma delta 4 may be the main precursor accounting for the increased production of urinary Adiol G in women with IH, in whom hirsutism may be due to a high 5 alpha-reductase activity. Indeed, 5 alpha-reductase as measured in vitro in pubic skin was significantly higher in hirsute patients (224 +/- 66 fmol/mg skin X h) than in normal women (45 +/- 15 fmol/mg skin X h).

Adolescent↗
PubMed1986

Progestin effect on cell proliferation and 17 beta-hydroxysteroid dehydrogenase activity in normal human breast cells in culture.

In contrast to cancer cell lines, normal human breast epithelial cells are infrequently studied. Such cells, now routinely cultured in our laboratory from tissue obtained at the time of reduction mammoplasty, were used to study the actions of estradiol (E2), the progestin promegestone (R5020), and the antiprogesterone RU486 on cell growth and progesterone-dependent 17 beta-hydroxysteroid dehydrogenase (E2DH) activity, which is considered good marker of epithelial differentiation as well as progesterone dependency. The studies were carried out using secondary cultures to assure equal initial cell distribution. Cell growth was estimated daily by a histometric method providing a growth index and DNA assay. E2 stimulation of cell growth was not found when the cells were grown in our usual culture medium, but E2 dose-dependent growth stimulation occurred in medium minimally supplemented with serum (1%), insulin; and epidermal growth factor. R5020 inhibited cell growth and stimulated E2DH activity in a dose-dependent manner. RU486 behaved as a pure but low potent progestin agonist concerning E2DH stimulation, but as an agonist with partial antagonist properties concerning cell growth inhibition. In conclusion, E2 stimulated proliferation of human breast epithelial cells in culture, whereas the progestin R5020 inhibited cell multiplication and favored differentiation. The antiprogesterone RU486 had a biphasic effect acting both as progestin agonist and partial antagonist.

17-Hydroxysteroid Dehydrogenases↗
PubMed1986

[Estradiol-progesterone interaction in normal and pathological human breast cells].

In most target tissues of the female genital tract, an adequate cell differentiation can be obtained with the successive and synergistic action of estradiol (E2) and progesterone (P), essentially because the progesterone receptor (PR) synthesis implicates the previous action of E2 via its E2 receptor (ER). In normal breast, E2 stimulates the growth of the ductal system whereas the development of acini depends on P secretion. In other words, when E2 plus P are secreted by the ovaries in balanced proportions, the two hormones permit a complete and harmonious development of the mammary gland. The antiestrogenic activity of P is carried out through the decrease of ER resynthesis and stimulation of 17 beta-hydroxysteroid dehydrogenase enzyme activity, which transforms E2 into its less active metabolite estrone (E1) in the target cells. These biochemical events are well documented concerning the endometrium. They have also been observed in normal mammary cells in primary cultures as well as in breast fibroadenomas with high epithelial cellularity. Moreover, data from literature indicate that E2 could be both a direct and indirect factor of cell multiplication in cancerous cell lines. P as well as progestins have the opposite effect. Recent results from this laboratory indicate that E2 and P also have antagonistic effects on the cell multiplication of normal human mammary cells in primary culture. Therefore, the hypothesis that a lack of P during a long period of the female genital like could be a factor in the promotion of breast cancer must be considered.

17-Hydroxysteroid Dehydrogenases↗
PubMed1985

[Induction of ovulation by a luteinizing hormone releasing hormone pump. Principles, indications and results].

A new treatment of hypothalamic amenorrhea is based mainly on Knobil's data demonstrating the physiological pulsatile secretion of GnRH. This hormone can be administered intravenously in a chronic intermittent (pulsatile) fashion. Nine women suffering from hypothalamic amenorrhea received 1 pulse of GnRH 5 to 20 micrograms every 90 minutes via a portable infusion pump. Nine pregnancies were induced after a mean 1.5 cycle. Three precocious miscarriages occurred. At this moment two children are born and four other pregnancies are undelivered. Venous tolerance was excellent, except in one patient who developed repeated venitis. Pulsatile administration of GnRH is very effective in inducing ovulation without risk of hyperstimulation frequently observed with HMG-hCG.

Abortion, Spontaneous↗
PubMed1985

Embryonic testicular regression syndrome and severe mental retardation in sibs.

The embryonic testicular regression syndrome associated with severe mental retardation is reported in three 46,XY sibs each of whom has a 46,XY chromosome complement. A fourth sib, a sister, also is severely retarded mentally; her chromosome complement is 46,XX. The 46,XY individuals, who were raised as females, presented varying degrees of genital ambiguity, indicating that their gonadal activities had been arrested at different times during embryogenesis. No trace of gonadal tissue could be found in either patient. The coincidence of the embryonic testicular regression syndrome and severe mental retardation in the same sibship is discussed.

Adult↗
PubMed1984

[Gonadoliberin. Therapeutic prospects].

Since the luteinizing hormone-releasing hormone (LH-RH) has been identified and its mode of action understood, it has become possible to envisage a therapeutic use of long-acting, non toxic analogues. Biochemical modifications of the decapeptide have resulted in the synthesis of potent LH-RH antagonists and agonists. Paradoxically, however, the agonists, devised to induce ovulation, exert an antagonistic action due to a decrease in the number of pituitary LH-RH receptors and to desensitization of the pituitary gland to the decapeptide. These inhibitory effects are associated with the prolonged activity of the analogues, in contrast with the stimulant effects of physiological LH-RH which has a short half-life and is secreted by bursts. The direct action of LH-RH analogues on gonads suggested by animal experiments has not been found in man since human gonads are devoid of specific LH-RH receptors. Alterations in steroid production are consecutive to the rise in LH initially induced by LH-RH agonists. The complete gonadotropic inhibition which follows the administration of LH-RH antagonists or agonists suggests that these compounds could be used in man, notably for the treatment of hormone-dependent carcinomas and isosexual early puberty and in the field of contraception.

Animals↗
PubMed1984

17 beta-Hydroxysteroid dehydrogenase activity in human breast epithelial cell and fibroblast cultures.

Primary cultures of human breast cells prepared from surgical specimens of reduction mammoplasty were used to study the activity of the enzyme 17 beta-hydroxysteroid dehydrogenase (E2DH) which converts estradiol (E2) into its less active metabolite estrone. This study was performed in both epithelial and stromal cells separated, after collagenase digestion of the tissue, on a Percoll gradient, and then cultured as monolayers in Ham's F 10 medium supplemented differently for epithelial cells and fibroblasts. E2DH activity was strikingly higher in epithelial cells than in fibroblasts, since after [3H]E2 incubation (2 nM), 600 fmol/micrograms DNA were metabolized to estrone in epithelial cells after 1 h, whereas an equivalent amount was hardly obtained in fibroblast cultures after 24 h. The affinity and capacity of E2DH were greater in epithelial cells with apparent Michaelis-Menten constant (Km) = 0.6 +/- 0.1 microM and maximum velocity (Vmax) = 250 to 360 pmol/micrograms DNA/h, whereas they were 10 +/- 1 microM and 50 to 70 pmol/micrograms DNA/h, respectively, in fibroblast cultures. Moreover, the E2DH activity was 2 to 5 times higher in epithelial cells cultured in the presence of the progestin medroxyprogesterone acetate, whereas it remained unchanged in fibroblasts cultured under the same conditions. This increase in E2DH activity was dose dependent from 10(-10) to 10(-7) M medroxyprogesterone acetate and inhibited by both actinomycin D and cycloheximide. This system of differential breast cell culture appears to be a fruitful tool for the study of the hormone dependence of normal breast growth and differentiation. Due to the presence of E2DH, epithelial cells are more apt to undergo and to moderate E2 action. Moreover, epithelial cells are a possible site of progesterone modulation of E2DH activity. Therefore, E2DH could be a good marker both for epithelial cells and their hormone dependence.

17-Hydroxysteroid Dehydrogenases↗