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ABSTRACT
The aim of this study was to examine the inhibitory effect of the non-aromatizable androgens on FSH-stimulated aromatase activity in porcine granulosa cells. The cells were isolated from medium-sized follicles (4–6 mm) of prepubertal pigs, and cultured under chemically defined conditions in the presence of FSH (1 μg/ml, NIADDK-oFSH-S13) with and without the androgens for an initial 48-h induction period. Subsequently, the spent medium was replaced with fresh medium containing only testosterone as substrate and the cells were reincubated for a further 6 h. The conversion of this steroid to oestradiol-17β during this latter 'test' period was taken as a measure of the aromatase activity. The addition of 5α-dihydrotestosterone (DHT) into cultures of FSH-stimulated cells during the induction period resulted in a definite dose-dependent inhibition (30–70%) of the aromatase activity expressed in the test period. This inhibitory action, of the mixed non-competitive type, is characterized by a decrease in the apparent V max and an increase in the K m value, suggestive of an androgen inhibition of FSH-stimulated aromatase synthesis. This inhibition was also shown by the other 5α- and 5β-reduced androgens: 5β-androstanedione was the most effective, while DHT was the least. Other steroids such as pregnenolone and progesterone were inhibitory, but testosterone and diethylstilboestrol were stimulatory. These results suggest an important mechanism for the intrafollicular control of oestrogen synthesis, involving a possible reciprocal relationship between aromatase and 5α-reductase activities.
J. Endocr. (1986) 108, 335–341
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Departments of Biochemistry and Biomedical Sciences, Pediatrics, Obstetrics and Gynecology, McMaster University, 1280 Main Street West HSC 4H30A, Hamilton, Ontario, Canada L8S 4K1
Departments of Biochemistry and Biomedical Sciences, Pediatrics, Obstetrics and Gynecology, McMaster University, 1280 Main Street West HSC 4H30A, Hamilton, Ontario, Canada L8S 4K1
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There is now considerable epidemiological and experimental evidence indicating that early-life environmental conditions, including nutrition, affect subsequent development in later life. These conditions induce highly integrated responses in endocrine-related homeostasis, resulting in persistent changes in the developmental trajectory producing an altered adult phenotype. Early-life events trigger processes that prepare the individual for particular circumstances that are anticipated in the postnatal environment. However, where the intrauterine and postnatal environments differ markedly, such modifications to the developmental trajectory may prove maladaptive in later life. Reproductive maturation and function are similarly influenced by early-life events. This should not be surprising, because the primordial follicle pool is established early in life and is thus vulnerable to early-life events. Results of clinical and experimental studies have indicated that early-life adversity is associated with a decline in ovarian follicular reserve, changes in ovulation rates, and altered age at onset of puberty. However, the underlying mechanisms regulating the relationship between the early-life developmental environment and postnatal reproductive development and function are unclear. This review examines the evidence linking early-life nutrition and effects on the female reproductive system, bringing together clinical observations in humans and experimental data from targeted animal models.
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SUMMARY
The distribution of water, electrolyte composition (Na, K, Ca, Mg, PO4, Cl) and extracellular fluid volume of eels (Anguilla anguilla L.) were investigated under different experimental conditions.
Adrenalectomy of the freshwater eel was followed by an increase in body weight, a fall in the amount and concentration of sodium in serum and muscle and a shift of water into the cells. The concentration of serum potassium remained within the normal range. Adrenalectomy of the sea-water eel was followed by a decrease in body weight and an increase in the concentration of extra- and intracellular sodium. The concentration of serum calcium also increased, that of potassium remained within the normal range but the actual content diminished.
Removal of the corpuscles of Stannius from the freshwater eel gave some effects similar to adrenalectomy. There was, however, no significant increase in body weight but the concentrations of serum potassium and calcium rose. Removal of the corpuscles from the sea-water eel brought about changes similar to, but less pronounced than those after adrenalectomy. The results of the injection of mammalian corticotrophin, cortisol, aldosterone and anti-aldosterone compounds are given. They are discussed in the light of the possible roles of the adrenal cortex and the corpuscles of Stannius in the maintenance of homeostasis of the eel in different environments.
Chemical Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China
Department of Biology, Xiamen University, Xiamen, People’s Republic of China
Molecular Pathology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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Chemical Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China
Department of Biology, Xiamen University, Xiamen, People’s Republic of China
Molecular Pathology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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Chemical Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China
Department of Biology, Xiamen University, Xiamen, People’s Republic of China
Molecular Pathology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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Chemical Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China
Department of Biology, Xiamen University, Xiamen, People’s Republic of China
Molecular Pathology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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Chemical Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China
Department of Biology, Xiamen University, Xiamen, People’s Republic of China
Molecular Pathology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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Chemical Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China
Department of Biology, Xiamen University, Xiamen, People’s Republic of China
Molecular Pathology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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Chemical Pathology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China
Department of Biology, Xiamen University, Xiamen, People’s Republic of China
Molecular Pathology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
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Conversion of cholesterol to biologically active steroids is a multi-step enzymatic process. Along with some important enzymes, like cholesterol side-chain cleavage enzyme (P450scc) and 3β-hydroxysteroid dehydrogenase/isomerase (3β-HSD), several proteins play key role in steroidogenesis. The role of steroidogenic acute regulatory (StAR) protein is well established. A novel protein, BRE, found mainly in brain, adrenals and gonads, was highly expressed in hyperplastic rat adrenals with impaired steroidogenesis, suggesting its regulation by pituitary hormones. To further elucidate its role in steroidogenic tissues, mouse Leydig tumor cells (mLTC-1) were transfected with BRE antisense probes. Morphologically the BRE antisense cells exhibited large cytoplasmic lipid droplets and failed to shrink in response to human chorionic gonadotropin. Although cAMP production, along with StAR and P450scc mRNA expression, was unaffected in BRE antisense clones, progesterone and testosterone yields were significantly decreased, while pregnenolone was increased in response to human chorionic gonadotropin stimulation or in the presence of 22(R)OH-cholesterol. Furthermore, whereas exogenous progesterone was readily converted to testosterone, pregnenolone was not, suggesting impairment of pregnenolone-to-progesterone conversion, a step metabolized by 3β-HSD. That steroidogenesis was compromised at the 3β-HSD step was further confirmed by the reduced expression of 3β-HSD type I (3ß-HSDI) mRNA in BRE antisense cells compared with controls. Our results suggest that BRE influences steroidogenesis through its effects on 3β-HSD action, probably affecting its transcription.
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Removal of the corpuscles of Stannius from the European eel (Anguilla anguilla L.) is followed by a fall in the concentration of plasma sodium and a rise in that of potassium and of calcium (Fontaine, 1964; Chester Jones, Henderson & Butler, 1965). It seemed possible that the corpuscles secrete corticosteroids, possibly aldosterone (Fontaine, 1963; Leloup-Hatey, 1964). A large quantity of corpuscles were therefore analysed for steroidogenetic capacity.
Fresh viscera from about 5000 eels, when gutted alive for commercial purposes, were obtained in Billingsgate Market. The corpuscles, a ventral pair on the posterior kidney, were removed in the Department of Zoology, St Bartholomew's Hospital Medical School, where the preliminary experiments were done.
Four experiments were carried out consisting of incubation of chopped corpuscles in a shaking incubator under air at 37° for 3 hr. The medium, isotonic with eel plasma, is given by Sandor et al. (1965). The substrate was a
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Abstract
H2N,d-Arg,Pro,Lys,Pro,d-Phe,Gln,d-Trp,Phe,d-Trp,Leu, Leu,NH2 (L-756,867), a weak substance P antagonist, inhibited L-692,429-stimulated GH release from rat primary pituitary cells in a dose-dependent manner. At a concentration of 50 nm, L-756,867 shifted the dose–response curve of L-692,429-induced GH release to the right by about tenfold. It also impaired the ability of L-692,429 to potentiate the effect of growth hormone-releasing factor (GRF) on GH release. Substance P (1 μm) had no effect on basal or L-692,429-stimulated GH release. When tested in anesthetized rats, L-756,867 inhibited L-692,429- and growth hormone-releasing hexapeptide- (GHRP-6)-stimulated GH secretion in a dose-dependent manner. Complete inhibition was observed at an i.v. dose of 100 μg/kg of L-756,867. However, at the same concentration, it had no effect on GRF-induced GH secretion. d-Lys3-GHRP-6, a GHRP-6 antagonist, had no effect on GHRP-6 or L-692,429-induced GH secretion even at an i.v. dose of 2 mg/kg. These results indicate that L-692,429 and GHRP-6 stimulate GH release both in vitro and in vivo via a common receptor and signaling pathway which is different from that of substance P in spite of the fact that their effects are inhibited by a weak substance P antagonist.
Journal of Endocrinology (1997) 152, 155–158
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SUMMARY
Extracts of corpuscles of Stannius from the silver eel have been shown to contain a substance with a powerful pressor action on intravenous injection into the rat. This material resembles mammalian renin in being non-diffusible through cellophane, heat-labile, and destroyed by acidification to pH 2. The effect in the rat differs, however, from that produced by mammalian renin in being more prolonged, and frequently biphasic.
Pressor activity has also been demonstrated in extracts of kidneys from freshwater silver eels. Incubation of kidney extract with mammalian renin-substrate produced an angiotensin-like pressor substance.
Both renal and corpuscular extracts had a prolonged pressor effect on intravenous injection into the eel. The identities of these pressor materials have not been finally established.
Removal of the corpuscles of Stannius from freshwater silver eels was followed by a drop in blood pressure to levels normally found in eels adapted to seawater.
The possible existence, in the eel, of a renin-angiotensin system analogous to that existing in mammals is discussed.
