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Biomedical subjects

G Verhoeven

Publications and source records attributed to G Verhoeven.

At least 163 records · Page 9Linked to original sources

Hormonal control of phosphodiesterase activity in cultured rat Sertoli cells.

Phosphodiesterase activity was studied in cultures derived from 19-day-old rats and enriched with Sertoli cells. Pretreatment of such cultures with follicle-stimulating hormone or L-isoproterenol increased cAMP-phosphodiesterase activity 5.2 and 2.0 times, respectively. cGMP-phosphodiesterase activity was not affected. Similar effects were observed in freshly isolated cells. The stimulatory effect was enhanced by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine and was mimicked by cholera toxin and dbcAMP. Increased activity was observed after a latent period of 1 h. Stimulation was blocked by cycloheximide and actinomycin D. The enzyme had an apparent Km for cAMP of 1.4 micro M. Its activity was enhanced by Mg2+ but not by Ca2+. It is concluded that phosphodiesterases play an important role in the hormonal control of Sertoli-cell function and may contribute to the refractory state of these cells after stimulation with various agonists.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Increased postovulatory plasma follicle stimulating hormone levels in the luteinized unruptured follicle syndrome: a role for inhibin?

In women who ovulated, the midcycle plasma follicle stimulating hormone (FSH) concentrations returned to basal concentrations within two days following the peak, whereas in women with a luteinized unruptured follicle, plasma FSH concentrations declined more slowly over a 4-5 day period. Since the peri- and postovulatory concentrations of plasma luteinizing hormone, prolactin, oestradiol-17 beta and progesterone were not significantly different between the two groups, we suggest that following the rupture of the Graafian follicle some substance in follicular fluid is resorbed from the peritoneal cavity which suppresses FSH secretion. Inhibin has biological properties which suggest it could be the substance involved.

Estradiol↗

Desensitization of cultured rat Sertoli cells by follicle-stimulating hormone and by L-isoproterenol.

When Sertoli cell-enriched cultures derived from 19-day-old Wistar rats are exposed to FSH or L-isoproterenol, cAMP accumulates in the medium. Previous contact of cultured cells with either one of these agents results in a reversible state of desensitization. During secondary stimulation up to 20 times less cAMP accumulates in the medium and in the cells. The extent of desensitization depends on the concentration of FSH or L-isoproterenol to which the cells have been exposed and on the duration of this previous contact. Pre-incubation with FSH results in cross-desensitization for L-isoproterenol. Comparable heterologous desensitization is not observed after pre-incubation with L-isoproterenol. This suggests that down-regulation of the respective receptors cannot be the only explanation. Refractoriness can also be induced by dbcAMP. This opens the possibility that cAMP itself contributes to the homologous and heterologous desensitization process.

1-Methyl-3-isobutylxanthine↗

Biochemical characterization of peritoneal fluid in women during the menstrual cycle.

Peritoneal fluid was collected at laparoscopy in women during the menstrual cycle and was assayed for protein and steroid hormone content. The total protein concentration in peritoneal fluid and the concentrations of the steroid hormone-binding proteins, transcortin and sex hormone-binding globulin, the polypeptide hormones, LH, FSH, and PRL, correlated with the plasma concentration but were lower; they were, respectively, 68%, 71%, 68%, 42%, and 34% of the plasma concentration. The concentrations of steroid hormones secreted by the ovary, i.e. 17 beta-estradiol, progesterone, androstenedione, and testosterone, were always equal or higher in peritoneal fluid than in plasma. In contrast, the concentrations of cortisol, a nonovarian steroid hormone, was 40% lower in peritoneal fluid than in plasma. No cyclic variations were observed in the peritoneal fluid concentrations of androstenedione and testosterone, two steroid hormones secreted by the stromal component of the ovary. On the contrary, the concentrations of 17 beta-estradiol and progesterone secreted by the follicular apparatus of the ovary increased sharply in peritoneal fluid after ovulation, reaching values of 44000 pg/ml and 3000 ng/ml, respectively. They declined progressively, whereas in plasma, peak concentrations were achieved only in the midluteal phase. In conclusion, the concentrations of 17 beta-estradiol and progesterone are much higher in peritoneal fluid than in plasma for at least 1 week after ovulation. We suggest that the secretion of the early, not yet vascularized, corpus luteum is directed preferentially toward the peritoneal cavity, creating a specific hormonal environment for the released oocyte and the oviduct.

Ascitic Fluid↗

Effect of different methods of germinal cell destruction on rat testis.

Germinal cell aplasia was induced in rats by heat sterilization, fetal irradiation or bilateral cryptorchidism. The influence of these treatments on the plasma concentraiton of LH and FSH, on the levels of sorbitol dehydrogenase and gamma-glutamyl transpeptidase (GTP) in the testis and on the weight of androgen target tissues was compared. All these methods damaged the germinal cells but also affected the other tubular cells and the interstitial compartment to a variable degree. Local heating affected plasma LH levels and GTP activity only minimally. Studies of GTP in cell-enriched fractions from the testes of rats with germinal cell aplasia indicated that this enzyme is not a Sertoli cell specific marker.

Animals↗

Influence of neonatal androgenization on the response of alpha 2u-globulin to testosterone and dexamethasone in the rat.

The influence of neonatal androgens on the response of alpha 2u-globulin to testosterone propionate or dexamethasone in adult rats has been investigated. It has been demonstrated previously that contact with androgens during the perinatal period results in higher unstimulated levels of alpha 2u-globulin in the serum of adult rats and in higher levels of this protein when the animals are stimulated either with androgens or glucocorticoids. As shown here, however, non-androgenized animals reached comparable serum levels to their neonatally androgenized litter-mates only during prolonged stimulation with testosterone propionate. Previous exposure to androgens during adulthood did not result in comparable differences in levels of alpha 2u-globulin in non-stimulated or stimulated rats. The residual sex difference in the stimulated levels observed in neonatally gonadectomized and oil-treated animals suggested that the sensitive period for this imprinting effect extends into the prenatal period.

Animals↗

[Simultaneous increase in the aromatization of testosterone into estrogens and secretion of inhibin by Sertoli cells in culture].

17 beta oestradiol and inhibin production by Sertoli cells has been investigated in vitro. In basal conditions, 17 beta-oestradiol secretion is weak whereas inhibin production is undetectable on days 7 and 9 of culture. Addition of PMSG (FSH-like gonadotrophin) and testosterone to the culture medium induces a simultaneous increase in 17 beta-oestradiol and inhibin production. PMSG alone has no effect neither on inhibin nor on 17 beta-oestradiol secretion. Testosterone alone significantly increases 17 beta-oestradiol and inhibin production. Human chorionic gonadotrophin (LH-like gonadotrophin) does not modify inhibin secretion. Dihydrotestosterone stimulates inhibin production without affecting oestrogens secretion. Thus, stimulation of aromatization of testosterone into 17 beta-oestradiol is associated with an increase of inhibin production, but this effect seems to be due to a direct action of androgens.

Animals↗

Stimulation effect of neurotransmitters on the aromatization of testosterone by Sertoli cell-enriched cultures.

The aromatization of testosterone has been studied in Sertoli cell-enriched cultures derived from 19-day-old rats. It was found that, besides dbcAMP and FSH, several neurotransmitters have a stimulatory effect. At a concentration of 10(-5) M, the strongest effects were noted with L-isoproterenol, L-norepinephrine, L-epinephrine and D,L-synephrine. Some stimulation was observed with dopamine, whereas histamine, melatonin and serotonin as well as acetylcholine and pilocarpine were ineffective. Experiments with alpha- and beta-adrenergic antagonists suggest that beta 2- and maybe also alpha-receptors are involved. The same maximal level of stimulation was generally observed for dbcAMP, FSH and isoproterenol. No further increase in activity was obtained with combinations of these compounds. It is concluded that adrenergic agonists may play a role in testicular development and function.

Animals↗

Relationship between the pituitary gland and gonadal steroids: involvement of a hypophysial factor in reduced alpha 2u-globulin and increased transcortin concentrations in rat serum.

Evidence is presented that the level of alpha 2u-globulin in the serum of male rats depends, at least in part, on neonatal androgens. After castration of adult animals the concentration of this protein falls but remains measurable, whereas in intact or ovariectomized female rats alpha 2u-globulin cannot be detected. Moreover, alpha 2u-globulin is found in adult male and female rats gonadectomized at birth and treated with a single injection of testosterone propionate immediately thereafter. The mechanism by which neonatal androgens increase the concentration of alpha 2u-globulin has been investigated. Transplantation of a supplementary pituitary gland under the renal capsule of male rats resulted in reduced levels of alpha 2u-globulin and increased levels of transcortin. The changes discussed here were observed only in those animals in which the transplant was functional and they were amplified or reversed by modulators of prolactin secretion such as oestrogens or bromocriptine respectively. The hypothesis is advanced that neonatal androgens stimulate the production of a hypothalamic inhibitory factor that controls the secretion of prolactin, or another hypophysial hormone subjected to similar neuroendocrine control. Measurements in gonadectomized animals and in rats receiving both oestradiol benzoate and bromocriptine indicate that, besides these pituitary-mediated effects, both oestrogens and androgens exert direct effects on the level of alpha 2u-globulin.

Alpha-Globulins↗