Activité gonadotrope d'un extrait d'urines de femmes en ménopause

Summary An extract from pooled postmenopausal urine has been investigated for its gonadotrophic activity. Dose-response curves have been constructed for its total gonadotrophic activity (stimulation of estrogen secretion as reflected by the uterine weight increase in immature mice) and for its ICSH activity (stimulation of androgen secretion as reflected by the ventral prostate weight increase in hypophysectomised immature rats). In hypophysectomised immature rats, the extract produced repair of the interstitial cells of the testes and complete spermatogenesis. It contains, therefore, FSH as well as ICSH activity in comparable amounts, a fact which opens up interesting therapeutic possibilities.     

Activité gonadotrope d'un extrait d'urines de femmes en ménopause

Summary In agreement with earlier observations on hypophysectomized male rats, a purified extract from pooled menopausal urine has been shown to contain follicle-stimulating (FSH) as well as luteinizing (LH) activity. Its administration to immature hypophysectomized female rats increased ovarian and uterine weights and induced follicle growth and the formation of corpora lutea. If the activity of the extract is measured in standardized units by bioassay in intact female mice using the uterine weight, the dose needed for corpus luteum formation in the hypophysectomized female rat seems to be approximately ten times higher than the dose producing interstitial cell repair and complete spermatogenesis in the hypophysectomized male.

---

---

2^e Communication: Effets sur les ovaires de rates impubères hypophysectomisées.     

Hormonal control of Sertoli cell metabolism regulates spermatogenesis

Hormonal regulation is essential to spermatogenesis. Sertoli cells (SCs) have functions that reach far beyond the physical support of germ cells, as they are responsible for creating the adequate ionic and metabolic environment for germ cell development. Thus, much attention has been given to the metabolic functioning of SCs. During spermatogenesis, germ cells are provided with suitable metabolic substrates, in a set of events mediated by SCs. Multiple signaling cascades regulate SC function and several of these signaling pathways are hormone-dependent and cell-specific. Within the seminiferous tubules, only SCs possess receptors for some hormones rendering them major targets for the hormonal signaling that regulates spermatogenesis. Although the mechanisms by which SCs fulfill their own and germ cells metabolic needs are mostly studied in vitro, SC metabolism is unquestionably a regulation point for germ cell development and the hormonal control of these processes is required for a normal spermatogenesis.     

Protein kinase CK2 and new binding partners during spermatogenesis

Protein kinase CK2 is an ubiquitously expressed enzyme that is absolutely necessary for the survival of cells. Besides the holoenzyme consisting of the regulatory β-subunit and the catalytic α- or α′-subunit, the subunits exist in separate forms. The subunits bind to a number of other cellular proteins. We show the expression of individual subunits as well as interaction with the transitional nuclear protein TNP1 and with the motor neuron protein KIF5C during spermatogenesis. TNP1 is a newly identified binding partner of the α-subunit of CK2. CK2α and KIF5C were found in late spermatogenesis, whereas CK2β and TNP1 were found in early spermatogenesis. CK2α, CK2α′, TNP1, and KIF5C were detected in the acrosome of spermatozoa, while CK2β was detectable in the mid-piece. Combinations of CK2 subunits might determine interactions with other proteins during spermatogenesis. KIF5C as a kinesin motor neuron protein is probably involved in the redistribution of proteins during spermatogenesis.     

Source of the tentacular hormone in terrestrial pulmonates

Summary Collar cells around the optic tentacles of pulmonate gastropods were shown to have a stimulating effect on spermatogenesis in vivo and in vitro. No hormonal action was found in the tentacles other than in collar cells. Therefore, collar cells are considered to be the source of the so-called tentacular hormone in stylommatophoran pulmonates. We propose to name the collar cell group optic gland.     

Molecular mechanisms in male determination and germ cell differentiation

Sex determination and gametogenesis are key processes in human reproduction, and any defect can lead to infertility. We describe here the molecular mechanisms of male sex determination and testis formation; defects in sex determination lead to a female phenotype despite the presence of a Y chromosome, more rarely to a male phenotype with XX chromosomes, or to intersex phenotypes. Interestingly, these phenotypes are often associated with other developmental malformations. In testis, spermatozoa are produced from renewable stem cells in a complex differentiation process called spermatogenesis. Gene expression during spermatogenesis differs to a surprising degree from gene expression in somatic cells, and we discuss here mechanistic differences and their effect on the differentiation process and male fertility.Received 23 January 2004; received after revision 30 March 2004; accepted 6 April 2004     

Arginine-vasotocin and gonadal activity in the lizard,Podarcis s. sicula Raf.

Summary Arginine-vasotocine (AVT) injected into male adult lizards,Podarcis s. sicula Raf., inhibits the last phases of spermatogenesis and the endocrine activity of gonads. In female lizards the substance induces an early interruption of egg deposition.     

Effect of retinyl acetate feeding on the activity of testicular enzymes in young rats

Summary Feeding of excess vitamin A significantly increased the activity of -galactosidase and -glucuronidase without effecting the activity of acid and alkaline phosphatase in rat testicular homogenates. It is suggested that imbalance of vitamin A affects the normal process of spermatogenesis by altering the activity of lysosomal enzymes.Acknowledgments. The author is grateful to Dr C.M. Singh, I.V.R.I., Izatnagar and Dr L.N. Singh, for providing facilities and encouragement and to Prof. O. Isler, Hoffmann-La Roche, Basel, Switzerland, for the generous supply of retinyl acetate used in this work.     

Fank1 interacts with Jab1 and regulates cell apoptosis via the AP-1 pathway

Regulation of apoptosis at various stages of differentiation plays an important role in spermatogenesis. Therefore, the identification and characterisation of highly expressed genes in the testis that are involved in apoptosis is of great value to delineate the mechanism of spermatogenesis. Here, we reported that Fank1, a novel gene highly expressed in testis, functioned as an anti-apoptotic protein that activated the activator protein 1 (AP-1) pathway. We found that Jab1 (Jun activation domain-binding protein 1), a co-activator of AP-1, specifically interacted with Fank1. Reporter analyses showed that Fank1 activated AP-1 pathway in a Jab1-dependent manner. Fank1 overexpression also increased the expression and activation of endogenous c-Jun. Further study showed that Fank1 inhibited cell apoptosis by upregulating and activating endogenous c-Jun and its downstream target, Bcl-3. This process was shown to be Jab1 dependent. Taken together, our results indicated that by interacting with Jab1, Fank1 could suppress cell apoptosis by activating the AP-1-induced anti-apoptotic pathway.     

Connexin 43 a check-point component of cell proliferation implicated in a wide range of human testis diseases

Gap junction channels link cytoplasms of adjacent cells. Connexins, their constitutive proteins, are essential in cell homeostasis and are implicated in numerous physiological processes. Spermatogenesis is a sophisticated model of germ cell proliferation, differentiation, survival, and apoptosis, in which a connexin isotype, connexin 43, plays a crucial role as evidenced by genomic approaches based on gene deletion. The balance between cell proliferation/differentiation/apoptosis is a prerequisite for maintaining levels of spermatozoa essential for fertility and for limiting anarchic cell proliferation, a major risk of testis tumor. The present review highlights the emerging role of connexins in testis pathogenesis, focusing specifically on two intimately interconnected human testicular diseases (azoospermia with impaired spermatogenesis and testicular germ cell tumors), whose incidence increased during the last decades. This work proposes connexin 43 as a potential cancer diagnostic and prognostic marker, as well as a promising therapeutic target for testicular diseases.     

5-Thio-d-glucose:o-diphenoloxidase inhibition as its mechanism of action

Summary 5-Thio-d-glucose completely inhibitedo-diphenoloxidase from animal as well as plant sources. It has been reported that thioglucose suppresses spermatogenesis in mice and also insect metamorphosis, probably through inhibition of glucose transport. Inhibition ofo-diphenoloxidase (which is active in spermatozoa and insect larvae) is suggested as an alternative mechanism of action of thioglucose.     

Zinc,copper and selenium in reproduction

Of the nine biological trace elements, zinc, copper and selenium are important in reproduction in males and females. Zinc content is high in the adult testis, and the prostate has a higher concentration of zinc than any other organ of the body. Zinc deficiency first impairs angiotensin converting enzyme (ACE) activity, and this in turn leads to depletion of testosterone and inhibition of spermatogenesis. Defects in spermatozoa are frequently observed in the zinc-deficient rat. Zinc is thought to help to extend the functional life span of the ejaculated spermatozoa. Zinc deficiency in the female can lead to such problems as impaired synthesis/secretion-of (FSH) and (LH), abnormal ovarian development, disruption of the estrous cycle, frequent abortion, a prolonged gestation period, teratogenicity, still-births, difficulty in parturition, pre-eclampsia, toxemia and low birth weights of infants. The level of testosterone in the male has been suggested to play a role in the severity of copper deficiency. Copper-deficient female rats are protected against mortality due to copper deficiency, and the protection has been suggested to be provided by estrogens, since estrogens alter the subcellular distribution of copper in the liver and increase plasma copper levels by inducing ceruloplasmin synthesis. The selenium content of male gonads increases during pubertal maturation. Selenium is localized in the mitochondrial capsule protein (MCP) of the midpiece. Maximal incorporation in MCP occurs at steps 7 and 12 of spermatogenesis and uptake dereases by step 15. Selenium deficiency in females results in infertility, abortions and retention of the placenta. The newborns from a selenium-deficient mother suffer from muscular weakness, but the concentration of selenium during pregnancy does not have any effect on the weight of the baby or length of pregnancy. The selenium requirements of a pregnant and lactating mother are increased as a result of selenium transport to the fetus via the placenta and to the infant via breast milk.     

Action des températures élevées sur la reproduction du planorbeBiomphalaria glabrata (gastéropode pulmoné)

Summary A temperature of 33°C increases growth of young snails but not that of adults. Adult fecundity is reduced and young snails do not reach sexual maturity. Oogenesis remains normal but late stages of spermatogenesis are scarce. The weight of the albumen gland in adult snails is increased, as is that of the albumen gland and the female part in young specimens. High temperatures, however, do not prevent differentiation of the genital apparatus but disturb its functioning.     

Copper metabolism in the LEC rat: Involvement of induction of metallothionein and disposition of zinc and iron

The Cu concentration was about 40 times higher in the liver of LEC (Long-Evans with a cinnamon-like coat color) rats aged 77 days (227.5±21.6 g/g liver) than in Fischer rats (5.2±0.1 g/g liver). However, in the kidney and brain of the LEC rats, Cu concentrations were lower than in these organs of the Fischer rats. Cu concentration in the hepatic metallothionein fraction was about 130 times higher in the LEC rats than in the Fischer rats. The LEC rats showed markedly low concentrations of Cu in the serum and bile. It seems likely that excretion of Cu from the liver into the bile and blood (as ceruloplasmin) is inherently lacking in the LEC rat.     

Genetic and histological aspects of stomach lesions induced by systemic injection of phenylbutazone in the rat

Roman high-avoidance (RHA/Verh) rats, food-deprived (F-D) for 5 days, had higher stomach lesion scores than did F-D Roman low-avoidance (RLA/Verh) rats. F-D RLA/Verh rats which were injected i.p. with phenylbutazone (PBZ) 24 h before examination, however, had higher scores than did PBZ-treated, F-D RHA/Verh rats. Histologically, extensive edema and cellular infiltration (including numerous erythrocytes) were seen below the lesions, in the submucosa, denoting vascular damage. An attenuating influence of food on the ulcerogenic effects of PBZ, which were much more severe in F-D than in fed rats, was also indicated.     

Heat stress response of male germ cells

The vast majority of mammalian testes are located outside the body cavity for proper thermoregulation. Heat has an adverse effect on mammalian spermatogenesis and eventually leads to sub- or infertility. Recent studies have provided insights into the molecular response of male germ cells to high temperatures. Here, we review the effects of heat on male germ cells and discuss the mechanisms underlying germ cell loss and impairment. We also discuss the role of translational control in male germ cells as a potential protective mechanism against heat-induced germ cell apoptosis.     

Genetic and pharmacological models of cholinergic supersensitivity and affective disorders

Summary Increased muscarinic sensitivity has been associated with altered hormonal states (hypothyroidism and hyperadrenocorticism), chronic administration of muscarinic antagonists or antidepressants with muscarinic actions, selective breeding for anticholinesterase sensitivity, and certain inbred strains of rats and mice. Thus, both genetic and environmental factors may influence muscarinic receptor sensitivity. The reasonably detailed studies on the selectively-bred rats have revealed that the Flinders Sensitive Line (FSL) rats weigh less, are less active, are more sensitive to muscarinic agonists and to stressors, and have higher concentrations of hippocampal and striatal muscarinic receptors than normal, or the selectively-bred, Flinders Resistant Line (FRL) rats. Thus, there are a number of parallels between FSL rats and depressed humans. The FSL rats may be the first animal model of depression to mimic the actual trait of depression, and not just the state.     

Genetic and histological aspects of stomach lesions induced by systemic injection of phenylbutazone in the rat

Summary Roman high-avoidance (RHA/Verh) rats, food-deprived (F-D) for 5 days, had higher stomach lesion scores than did F-D Roman low-avoidance (RLA/Verh) rats. F-D RLA/Verh rats which were injected i.p. with phenylbutazone (PBZ) 24 h before examination, however, had higher scores than did PBZ-treated, F-D RHA/-Verh rats. Histologically, extensive edema and cellular infiltration (including numerous erythrocytes) were seen below lesions, in the submucosa, denoting vascular damage. An attenuating influence of food on the ulcerogenic effects of PBZ, which were much more severe in F-D than in fed rats was also indicated.The authors thank K. Bättig and J. R. Martin for their assistance during the planning stages, B. Hauser, A. Waldvogel and P. Wild of the Veterinary Medical Faculty of Zurich University for preparing the histological sections and for the photography, and P. Elsinger for technical help.     

The biology of interleukin-1: emerging concepts in the regulation of the actin cytoskeleton and cell junction dynamics

Interleukin (IL)-1 is a proinflammatory cytokine with important roles in innate immunity, as well as in normal tissue homeostasis. Interestingly, recent studies have also shown IL-1 to function in the dynamics of the actin cytoskeleton and cell junctions. For example, treatment of different epithelia with IL-1α often results in the restructuring of the actin network and cell junctions, thereby leading to junction disassembly. In this review, we highlight new and interesting findings that show IL-1 to be a critical player of restructuring events in the seminiferous epithelium of the testis during spermatogenesis.     

Effect of adrenalectomy and dexamethasone treatment on the monoamine oxidase activity in the thyroid gland of the rat

Summary Adrenalectomy increased MAO activity in the thyroid gland of rats. The administration (200 g/100 g daily for 7 days) to adrenalectomized rats decreased MAO activity below levels of intact controls.