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Human pituitary FSH increased the incorporation of [5-3H]uridine into RNA in vivo in the testes of intact 9-day-old mice and of hypophysectomized adults. In both groups the effect was greatest 8 h after administration of 5–7·5 i.u. FSH. Autoradiographs were prepared from the testes of hypophysectomized adult mice given subcutaneous injections of FSH or of 0·9% saline 6 h, and [5-3H]uridine 1·5 h, before death. Treatment with FSH caused statistically significant increases in the density of silver grains over the nuclei of Sertoli cells, type A and intermediate spermatogonia, and preleptotene and mid-pachytene primary spermatocytes. It was concluded that FSH has a generalized stimulatory action on RNA synthesis in the nuclei of Sertoli cells and those types of germinal cell which synthesize RNA most actively.
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Hypophysectomized adult mice were given injections of highly purified FSH 12 h before killing, and of tritiated lysine or arginine 2 h before killing. Autoradiographs were prepared from paraffin wax sections of testes. Treatment with FSH increased the density of silver grains over the nuclei of the Sertoli cells and of all types of germinal cell except the early spermatids. The stimulatory effect of FSH on incorporation of both lysine and arginine was most marked in the nuclei of preleptotene primary spermatocytes. The ratio of arginine to lysine incorporation was greater in spermatids undergoing nuclear elongation than in other types of cell.
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In the Japanese quail gonadal steroids can depress plasma levels of LH and FSH. Since it is now accepted that testosterone metabolites may be metabolized to the tissue-active forms of the hormone, the in-vitro tissue incubation has been combined with steroid replacement therapy in vivo to investigate the physiological roles of various testosterone metabolites as inhibitory feedback agents on gonadotrophin secretion in quail. After the incubation of quail pituitary glands for 3 h with labelled testosterone four metabolites could be identified; androst-4-ene-3,17-dione, 5β-dihydrotestosterone (5β-DHT), 5β-androstane-3α,17β-diol and 5α-DHT. No 5α-androstane-3α,17β-diol was found. Quantitatively, androstenedione was the major metabolite and conversion of testosterone to 5β-metabolites was significantly greater than to 5α-androgens. Hypothalamic and hyperstriatal tissues converted testosterone to androstenedione, 5β-DHT and 5β-androstane-3α,17β-diol but not to 5α-DHT or 5α-androstane-3α,17β-diol.
Gonadotrophin secretion was studied in castrated quail after chronic s.c. implantation of steroid-containing silicone elastomer capsules or acute injection i.m. of steroid in ethanol: saline. Irrespective of the route of administration seven androgens, listed in descending order of potency, reduced the increased levels of plasma LH: testosterone; 5α-DHT; androstenedione; 5α-androstane-3,17-dione; 5α-androstane-3α,17β-diol; 5α-androstan-3α-ol-17-one; 5α-androstan-3β-ol-17-one. No changes in levels of plasma LH were observed after the administration of 5β-DHT, 5α-androstane-3β,17β-diol, 5βandrostane-3α,17β-diol, 5β-androstane-3,17-dione, androst-5-ene-3β,17β-diol or androst-5-en-3β-ol-17-one.
Testosterone and oestradiol-17β were effective in inhibiting secretion of both LH and FSH in young photostimulated quail and completely blocked testicular growth: 5α-DHT inhibited only the release of LH and testicular growth was unaffected.
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SUMMARY
Studies on the mode of action of tamoxifen have shown that this compound ultimately causes regression of mammary tumours induced in female rats by 7,12-dimethylbenz(a)-anthracene, but induces preliminary effects similar to those produced by oestradiol-17β. Following a single intravenous injection of either substance, a sequence of events was observed which included depletion of cytoplasmic receptor, a concomitant increase in nuclear receptor and a subsequent replenishment of cytoplasmic receptor. Tamoxifen and oestradiol-17β induced a transient increase in RNA polymerase B activity, followed by increases in RNA polymerase A and, again, RNA polymerase B activity. Tamoxifen, unlike oestradiol-17β, could not maintain replenishment of cytoplasmic receptor, the increase in RNA polymerase A activity or the secondary rise in RNA polymerase B activity. The basic anti-oestrogenic properties of tamoxifen may be implicit in its inability to maintain oestrogenic stimulation, and may be linked to its retention time within the nuclei.
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A cloacal gland complex whose growth and development is androgen-dependent exists in the Japanese quail. In-vitro incubation studies of the cloacal gland using 4-14C-labelled testosterone as substrate allowed the positive identification of five metabolites: androstenedione, 5β-dihydrotestosterone (5β-DHT), 5β-androstane-3α,17β-diol, 5α-DHT and 5α-androstane-3α,17β-diol. More polar metabolites, not yet chemically identified, were detected in trace amounts. Androstenedione appeared to be the main testosterone metabolite in immature birds while in mature birds on long daylengths testosterone was preferentially metabolized to 5α-DHT. This change may have been in response to the higher levels of plasma steroids found in mature birds. When various testosterone metabolites, contained in silicone elastomer capsules, were implanted s.c. into castrated birds maintained on a photostimulatory light régime, 5α-DHT, 5α-androstane-3,17-dione, androstenedione and 5α-androstan-3α-ol-17-one were shown to be equipotent with testosterone in stimulating the development of the cloacal gland. 5α-Androstane-3α,17β-diol and 5α-androstan-3β-ol-17-one stimulated some growth while 5β-DHT, 5α-androstane-3β,17β-diol, 5α-androstane-3α,17β-diol, 5β-androstane-3,17-dione, androst-5-en-3β-ol-17-one and androst-5-ene-3β,17β-diol were completely ineffective.
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ABSTRACT
Interleukin-6 (IL-6) has actions on a variety of endocrine tissues. The cytokine is secreted by cells of the anterior pituitary and endocrine pancreas and has recently been shown to be produced by cultures of thyroid epithelial cells. In this study we have examined some of the factors which regulate IL-6 release from an immortalized human thyroid line (HTori3).
IL-6 release over 24 h was stimulated by TSH (5000 μU/ml), by forskolin (0·01 mmol/l), by fetal calf serum (1–20%) and by epidermal growth factor (20 ng/ml). Stimulation was also apparent with γ-interferon and with tumour necrosis factor at concentrations known to enhance class II major histocompatibility antigen expression by thyroid epithelium. The most potent factor tested was interleukin-1 (IL-1), which controls IL-6 release from other cell types. Threefold stimulation was found with 1 U/ml rising to 350-fold with 1000 U/ml. The effect of IL-1 took 2 h to develop and was blocked by cycloheximide (100 μmol/l). Stimulation was not markedly inhibited by pertussis toxin. Many of the actions of IL-1 are mediated by prostaglandin E2 (PGE2). At concentrations as low as 30 nmol/l, PGE2 stimulated IL-6 release but the maximum stimulation obtained with PGE2 was only threefold. The effect of IL-1 was not inhibited by indomethacin.
These data provide further evidence that IL-6 is produced by human thyrocytes. The effect of IL-1 has not been demonstrated previously. Stimulation of IL-6 release by IL-1 did not appear to be mediated by prostaglandin. IL-6 may influence hormone release from the thyroid as it does in other tissues. High concentrations of IL-6 in the thyroid may increase infiltration by, and activation of, lymphocytes in patients with autoimmune thyroid disease.
Journal of Endocrinology (1992) 133, 477–482
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ABSTRACT
Subconfluent human thyroid cells in monolayer, isolated from thyrotoxic tissue or non-toxic goitres obtained at surgery, responded to the addition of epidermal growth factor (EGF) with an increase in cell growth as measured by increased incorporation of [3H]thymidine into trichloroacetic acid-precipitable material. The growth response to EGF was concentration-dependent and the characteristics of the responses were the same using EGF from murine or human sources. With concentrations which stimulated growth, EGF was found to inhibit human thyroid cell function as measured by the release of radioimmunoassayable tri-iodothyronine into the incubation medium. Thyrotrophin (TSH) was also found to stimulate human thyroid cell growth but at concentrations far lower than those used to stimulate thyroid cell function in this system. The effect of EGF on the differentiating action of TSH on human thyroid cells in culture was also investigated; the association of thyroid cells into two-dimensional follicular structures produced by the incubation of thyroid cells at a high cell density with TSH was found to be inhibited by the addition of EGF.
J. Endocr. (1986) 108, 393–398
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SUMMARY
Pregnant rabbits were treated with indomethacin (8–10 mg/kg/day) or dexamethasone (1·2–1·8 mg/kg/day) during late gestation. The effects of these treatments on the concentrations of progesterone and prostaglandin F (PGF) in the peripheral plasma, and the outcome of gestation were studied. Treatment with indomethacin significantly prolonged the length of gestation (P < 0·01) compared with control, untreated animals. In these treated animals, the plasma progesterone levels declined at a similar time to that in control rabbits but the increase in systemic PGF normally seen during late pregnancy was reduced. Dexamethasone treatment reliably induced premature delivery within 3–6 days. The plasma progesterone concentration fell rapidly during the first 24 h of dexamethasone administration, but in no animal was this associated with a significant increase in the plasma levels of PGF.
These results are consistent with the suggestion that prostaglandins are involved in the normal initiation of parturition in the rabbit. They do not support the hypothesis that the effect of dexamethasone on the length of gestation is mediated through an increase in the production of prostaglandin F.
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SUMMARY
Ovine luteinizing hormone (LH) (300 μg/day in divided subcutaneous doses) had a luteotrophic effect of limited duration in intact and hypophysectomized 10-day pseudopregnant rabbits (6–10 days in intact animals; 3–6 days in hypophysectomized animals). Higher dose levels caused reovulation in which case luteolysis occurred. Suppression of reovulation with anti-ovine follicle-stimulating hormone (FSH) serum permitted the daily dose of LH to be raised to 750 μg without causing luteolysis or reovulation. Anti-LH serum was luteolytic in the intact animals. A combination of ovine FSH (200 μg) and LH (300 μg) was indistinguishable from LH alone in terms of its luteotrophic effect in hypophysectomized 10-day pseudopregnant rabbits. Ovine FSH at large daily dose levels (1000 μg) was more effectively luteotrophic than LH alone in a significant number of animals for 10 days after hypophysectomy: endometrial changes in these animals resembled those only seen in normal pregnancy. The luteotrophic effect of 1000 μg FSH was believed to be dependent on a small but significant content of LH, estimated to be about 10 μg. Ovine FSH and anti-FSH serum in intact pseudopregnant rabbits had no detectable effect on luteal function. Animals hypophysectomized at the 7th day and treated with 300 or 500 μg LH/day showed no luteal maintenance for 6 days nor was reovulation induced. Sensitivity to the luteotrophic effect of LH was deemed, therefore, to be greater at 10 than at 7 days of pseudopregnancy. Endometrial criteria were found to be reliable indicators of luteal function. The appearance of ciliated cells was correlated with the decline of the corpora lutea. When reovulation occurred, a new progestational cycle was rapidly superimposed on the existing one.
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SUMMARY
Large doses of human chorionic gonadotrophin and human pituitary follicle-stimulating hormone were given singly and in combination to six eunuchoidal men. None had an increased excretion of urinary gonadotrophin before treatment.
Histological examination of the testicles showed very immature germinal epithelium in five of the patients before treatment. Spermatozoa were found histologically in three patients, only after combined treatment with both gonadotrophins. Low concentrations of spermatozoa appeared in semen from two of these patients.
One patient was found to have histological evidence of spermatogenesis before treatment but was unable to produce semen. Treatment with chorionic gonadotrophin alone enabled him to produce semen containing up to 15,000,000 spermatozoa per ml.
Significant increases were found in the urinary levels of a variety of steroids and in total body potassium after treatment with chorionic gonadotrophin and a variable amount of somatic development took place.
