Prolactin Is a Strong Candidate for the Regulation of Luteal Steroidogenesis in Vizcachas (Lagostomus maximus).

Prolactin (PRL) is essential for the maintenance of the corpora lutea and the production of progesterone (P4) during gestation of mice and rats, which makes it a key factor for their successful reproduction. Unlike these rodents and the vast majority of mammals, female vizcachas (Lagostomus maximus) have a peculiar reproductive biology characterized by an ovulatory event during pregnancy that generates secondary corpora lutea with a consequent increment of the circulating P4. We found that, although the expression of pituitary PRL increased steadily during pregnancy, its ovarian receptor (PRLR) reached its maximum in midpregnancy and drastically decreased at term pregnancy. The luteinizing hormone receptor (LHR) exhibited a similar profile than PRLR. Maximum P4 and LH blood levels were recorded at midpregnancy as well. Remarkably, the P4-sinthesizing enzyme 3ß-HSD accompanied the expression pattern of PRLR/LHR throughout gestation. Instead, the luteolytic enzyme 20α-HSD showed low expression at early and midpregnancy, but reached its maximum at the end of gestation, when PRLR/LHR/3ß-HSD expressions and circulating P4 were minimal. In conclusion, both the PRLR and LHR expressions in the ovary would define the success of gestation in vizcachas by modulating the levels of 20α-HSD and 3ß-HSD, which ultimately determine the level of serum P4 throughout gestation.

Quantification of healthy and atretic germ cells and follicles in the developing and post-natal ovary of the South American plains vizcacha, Lagostomus maximus: evidence of continuous rise of the germinal reserve.

The female germ line in mammals is subjected to massive cell death that eliminates 60-85% of the germinal reserve by birth and continues from birth to adulthood until the exhaustion of the germinal pool. Germ cell demise occurs mainly through apoptosis by means of a biased expression in favour of pro-apoptotic members of the BCL2 gene family. By contrast, the South American plains vizcacha, Lagostomus maximus, exhibits sustained expression of the anti-apoptotic BCL2 gene throughout gestation and a low incidence of germ cell apoptosis. This led to the proposal that, in the absence of death mechanisms other than apoptosis, the female germ line should increase continuously from foetal life until after birth. In this study, we quantified all healthy germ cells and follicles in the ovaries of L. maximus from early foetal life to day 60 after birth using unbiased stereological methods and detected apoptosis by labelling with TUNEL assay. The healthy germ cell population increased continuously from early-developing ovary reaching a 50 times higher population number by the end of gestation. TUNEL-positive germ cells were <0.5% of the germ cell number, except at mid-gestation (3.62%). Mitotic proliferation, entrance into prophase I stage and primordial follicle formation occurred as overlapping processes from early pregnancy to birth. Germ cell number remained constant in early post-natal life, but a remnant population of non-follicular VASA- and PCNA-positive germ cells still persisted at post-natal day 60. L. maximus is the first mammal so far described in which female germ line develops in the absence of constitutive massive germ cell elimination.

Ethnic variation of the P53 codon 72 polymorphism, HPV persistence, and cervical cancer risk.

Association between the p53 codon 72 polymorphism and cervical cancer remains unresolved. We determined the association between the polymorphism and risk of human papillomavirus (HPV) persistence. The polymorphism was detected by restriction enzyme digestion following p53 amplification and HPV detection by the PGMY 09/11 primer set followed by reverse line blot hybridization: 3371 samples were analysed. HPV persistence was assessed on a subset of samples collected at baseline, four and 10 months (n =442). Highly significant differences were observed between ethnic groups (P <0.005). No associations were found between P53 arginine and cytological grade in women infected with any HPV or any oncogenic HPV, despite adjustment for ethnicity. These results were sustained even when HPV-negative women were used as controls. Persistence for any or oncogenic HPV infection was not associated with the polymorphism, irrespective or ethnicity adjustment. Our findings do not support a role for this polymorphism conferring elevated risk for HPV-related disease.

Anti-inflammatory effects of theophylline: modulation of immune functions during murine leukemia virus infection.

LP-BM5 murine leukemia virus induces immune dysfunction leading to B cell leukemia and murine AIDS with cytokine dsyregulation. Theophylline induces apoptosis of leukemia cells in humans. Therefore the effects of theophylline on immune dysfunction in a murine model of leukemia were investigated. C57BL/6 mice consumed drinking water containing 0.3% theophylline beginning 2 weeks after murine retrovirus infection for 4 months. Theophylline largely prevented the retrovirus induced splenomagaly, lymphodenopathy, reduction in B and T cell proliferation, and suppression of Thl cytokines (IL-2) secretion. It also suppressed Th2 cytokine (IL-4, TNF-alpha, and IL-10) production, which was otherwise stimulated by retrovirus infection. These data suggest that immune dysfunction, induced by murine retrovirus infection, was largely prevented by theophylline treatment.

Immune dysfunction during alcohol consumption and murine AIDS: the protective role of dehydroepiandrosterone sulfate.

Acquired immune deficiency syndrome (AIDS) is a clinical disorder caused by the human immunodeficiency virus (HIV) after development of severe immunosuppressive changes. Chronic ethanol (EtOH) consumption accentuates the severity of murine AIDS (MAIDS). Because hormone production is often suppressed by chronic EtOH intake, as well as retrovirus infection, we investigated whether hormone supplementation during chronic EtOH consumption contributes to slowing immune dysfunction caused by LP-BM5 infection and/or EtOH use. Because dehydroepiandrosterone sulfate (DHEAS) was previously shown to have immune-enhancing properties during MAIDS, we determined whether DHEAS reduced cytokine dysregulation otherwise exacerbated by chronic EtOH intake during MAIDS. Adult female C57BL/6 mice were infected with LP-BM5 murine retrovirus. Some were fed 40% EtOH in drinking water and agar gel for 16 weeks postinfection. EtOH consumption further inhibited T- and B-cell proliferation beyond suppression due to retrovirus infection. Interleukin (IL)-2 release produced by concanavalin A-stimulated splenocytes was reduced by EtOH use by infected and uninfected mice. DHEAS overcame much of the effects induced by retrovirus infection and/or EtOH use. IL-4 secretion and IL-6 secretion were enhanced. Hepatic vitamin E levels were decreased by murine retrovirus infection, as well as by EtOH use in both uninfected and infected mice. In addition, DHEAS (0.01%) supplementation during MAIDS prevented the further dysregulation of cytokines and hepatic lipid peroxidation due to EtOH intake, partially restored T- and B-cell proliferation, and maintained hepatic vitamin E levels to near normal levels.

Prevention of immune dysfunction and vitamin E loss by dehydroepiandrosterone and melatonin supplementation during murine retrovirus infection.

Female C57BL/6 mice infected with the LP-BM5 leukaemia retrovirus developed murine acquired immune-deficiency syndrome (AIDS). Dehydroepiandrosterone (DHEA) and melatonin (MLT) modify immune dysfunction and prevent lipid peroxidation. We investigated whether DHEA and MLT could prevent immune dysfunction, excessive lipid peroxidation, and tissue vitamin E loss induced by retrovirus infection. Retrovirus infection inhibited the release of T helper 1 (Th1) cytokines, stimulated secretion of Th2 cytokines, increased hepatic lipid peroxidation, and induced vitamin E deficiency. Treatment with DHEA or MLT alone, as well as together, largely prevented the reduction of B- and T-cell proliferation as well as of Th1 cytokine secretion caused by retrovirus infection. Supplementation also suppressed the elevated production of Th2 cytokines stimulated by retrovirus infection. DHEA and MLT simultaneously reduced hepatic lipid peroxidation and prevented vitamin E loss. The use of DHEA plus MLT was more effective in preventing retrovirus-induced immune dysfunction than either DHEA or MLT alone. These results suggest that supplementation with DHEA and MLT may prevent cytokine dysregulation, lipid oxidation and tissue vitamin E loss induced by retrovirus infection. Similarly, hormone supplementation also modified immune function and increased tissue vitamin E levels in uninfected mice.

Injection of T-cell receptor peptide reduces immunosenescence in aged C57BL/6 mice.

Previous studies established that retrovirally infected young mice produced large amounts of autoantibodies to certain T-cell receptor (TCR) peptides whose administration diminished retrovirus-induced immune abnormalities. C57BL/6 young (4 weeks) and old (16 months) female mice were injected with these same synthetic human TCR V beta 8.1 or 5.2 peptides. Administration of these autoantigenic peptides to old mice prevent immunosenescence, such as age-related reduction in splenocyte proliferation and interleukin-2 (IL-2) secretion. TCR V beta peptide injection into young mice had no effect on T- or B-cell mitogenesis and IL-4 production while modifying tumour necrosis factor-alpha (TNF-alpha), IL-6, and interferon-gamma (IFN-gamma) secreted by mitogen-stimulated spleen cells. TCR V beta injection also retarded the excessive production of IL-4, IL-6 and TNF-alpha induced by ageing. These data suggest that immune dysfunction and abnormal cytokine production, induced by the ageing process, were largely prevented by injection of selected TCR V beta CDR1 peptides.

Dehydroepiandrosterone (DHEA) sulfate prevents reduction in tissue vitamin E and increased lipid peroxidation due to murine retrovirus infection of aged mice.

Dietary effects of dehydroepiandrosterone sulfate (DHEAS) supplementation on tissue antioxidants and lipids were investigated in retrovirus infected mice. DHEA is a powerful antioxidant and immunomodulator whose production declines with age. For this study, twenty-four female, 15-month-old C57BL/6 mice were left uninfected while twenty-four were infected with LP-BM5 murine leukemia virus, causing murine AIDS. The retroviral infection caused immune dysfunction and loss of hepatic and cardiac vitamins E and A, resulting in increased lipid peroxides. Treatment with DHEAS at 0.01 or 0.005% in drinking water for 10 weeks post-infection significantly (P < 0.05) lowered lipid peroxidation in both heart and liver tissues. Treatment with DHEAS also largely prevented loss of the antioxidants, such as vitamin E and A, and prevented loss of phospholipid in the hearts and livers of the old uninfected as well as infected mice. This study suggests that DHEAS supplementation reduces damage associated with elevated oxidation due to aging and retrovirus infection.

Modulation of cytokine production by dehydroepiandrosterone (DHEA) plus melatonin (MLT) supplementation of old mice.

Tissue levels of the antioxidants melatonin (MLT) and dehydroepiandrosterone (DHEA) decline with age, and this decline is correlated with immune dysfunction. The aim of the current study is to determine whether hormone supplementation with MLT and DHEA together would synergize to reverse immune senescence. Old (16.5 months) female C57BL/6 mice were treated with DHEA, MLT, or DHEA + MLT. As expected, splenocytes were significantly (P < 0.05) higher in old mice as compared to young mice. DHEA, MLT, and DHEA + MLT significantly (P < 0.005) increased B cell proliferation in young mice. However, only MLT and DHEA + MLT significantly (P < 0.05) increased B cell proliferation in old mice. DHEA, MLT, and DHEA + MLT help to regulate immune function in aged female C57BL/6 mice by significantly (P < 0.05) increasing Th1 cytokines, IL-2, and IFN-gamma or significantly (P < 0.05) decreasing Th2 cytokines, IL-6, and IL-10, thus regulating cytokine production. DHEA and MLT effectively modulate suppressed Th1 cytokine and elevated Th2 cytokine production; however, their combined use produced only a limited additive effect.

Melatonin, immune modulation and aging.

Melatonin is a hormone secreted by the pineal gland in response to photoperiods and influences many important biological processes. For one, Melatonin has been shown to produce resistance to cancer and infectious diseases in aged animals. Studies in animals have demonstrated melatonin-related mechanisms of action on immunoregulation. Additionally, melatonin has been successfully used in humans, along with interleukin-2, as a treatment of solid tumors. In vivo and in vitro studies show melatonin enhances both natural and acquired immunity in animals. Despite all of this intriguing evidence, melatonin's mechanism of action on the immune system is only partially defined. It does, however, appear to act through lymphocyte receptors, and perhaps, receptors on other immune tissues, to modulate immune cells. In order to understand immunomodulation and anti-cancer effects, information on melatonin and it's interactions with other endocrine hormones are summarized.

The Kingdom of Belgium: country profile.

PIP: Focus in this discussion of Belgium is on: cities and regions, population change, households and families, labor force, consumption, communication and transport, and sources of information. Belgium was created in 1830 as a constitutional monarch and buffer state amidst great European powers. Its constitution creating a parliamentary system of government has served as a model for many emerging democracies. Unemployment dropped from more than 14% in 1984 to just over 12% in the 1st quarter of 1986. Belgium also is experiencing a somewhat improved balance of payments and respectable overall economic growth of around 2.5% through the 1st half of 1986 along with close trading links and minimum customs formalities with Luxembourg and Holland. Yet, wages lag behind inflation after the last government suspended an index system that mandated automatic income adjustments in line with the cost of living. In 1983, for the 1st time since the country's economic boom of the 1960s, purchasing power for the average Belgium declined. About 90% of Belgium's estimated 9,880,000 inhabitants live in cities and towns ranging over a territory of only 30,518 KM. Administratively, the region of Flanders has 5 provinces, Wallonia, 4. Regions are further broken down into arrondissements and communes. Belgium's under replacement level birth rate is expected to decline further, and its proportion of elderly persons in the total population is expected to rise, straining even further an already overburdened system of social security and health care. Belgium's 10-year intercensal population gain (between 1971-81) was the smallest in the country's history. Belgium's total population stood at 9,853,023 on January 1, 1984, a decline of almost 5000 from the preceding year. Belgium's average household size is decreasing due to a larger aged population, an upsurge in divorces and unmarried young couples, and a declining birth rate. About 1/3 of the population works. At mid-1984, the figure stood at 3,638,000. The service sector generates more than half the country's jobs. The largest share of household consumption in 1983 was on food, at 18.6%.^ieng

Sterilization on the rise in Britain.

PIP: According to the British 1983 Report of the General Household Survey (GHS), the 1st such survey to seek data on contraception, 3/4 of British women 18-44 years of age used some form of contraception in 1983. Oral contraceptives were the method of choice of 28% of respondents, although use of this method declines with age (only 4% among women 40-44 years of age). 22% of respondents either had been sterilized or were living with a sterilized partner. The percentage of married or formerly married women ages 16-39 years who were sterilized or had a sterilized partner rose from 4% in 1970 to 24% in 1983. The survey further found that 35% of women cohabitated before marriage. Another GHS finding shows decreased family size. Family size/household declined from 2.91 in 1971 to 2.64 in 1982. Over the same period, persons living alone increased from 6 to 23% of the total population, and single-parent families increased from 5% to 13% of the total.^ieng

Ile de France: the metro area of Paris.

PIP: Analysis of small area data shows that France is now experiencing the same trend seen in the 1970s in Great Britain and the US--the population in urban areas is migrating to semirural areas beyond traditional suburbs but still within commuting distance of city centers and employment. As a result, no population center of more than 20,000 people gained population between 1975 and 1982. The Ile de France Region houses 18.5% of France's total population, yet it accounts for only 2.2% of the country's land mass. This region grew by more than 194,400 residents between 1975 and 1982 to a total of 10 million people. For the 1st time in 20 years, the rate of population drain from the city center has slowed. Factors attributable to this slowing of population loss are 1) a sluggish economy holding down housing starts, 2) the aging of the population--making it less mobile, 3) a slight increase in births among inner-city Parisians, and 4) a shortage in older rental housing. Over the past 20 years Paris has lost 1/2 its blue collar jobs; it is becoming more and more bourgeois. The age and sex distribution of Ile de France reflects the effects of the World Wars and the postwar baby booms. One person households predominate in the Paris metro area; 2 person households declined from 30% in 1975 to 28% in 1982. In 1982, 42% of Paris residents were married couples, 8% were widows or widowers, 6% were divorced, and 44% were single. At least a half million Paris residents hold management or professional jobs; Paris produces half the area's jobs. Average salaries in Paris are more than 1/5 higher than the national average. 1/3 of France's students are enrolled in universities located in Paris. Nearly 15% of the French household budget is spent on health related services, and 1 in 5 Frenchman runs for aerobic exercise. Overall, Paris functions as the vital hub of a thriving metropolitan area, dominating the country's closely interrelated Ile de France region.^ieng

Grand Duchy of Luxembourg. Country profile.

PIP: This article provides a profile of Luxembourg, a country known for its high standard of living and social stability. The total fertility rate in Luxembourg in 1983 was 1.4. 26% of the population are immigrants. The total population of teh country stood at 364,602 in 1981 and is expected to decline to 349,000 by the year 2000 if present trends continue. Immigration is actively promoted to provide manual labor; about 30% of immigrants are from Portugal. The 1981 census counted 128,456 households in the country, with an average household size of 2.83 people. 24% of men over 18 years and 23% of women over 15 years have never married. Although only 19% of men over age 65 years are widowers, 55% of women in this age group are widows. About 50,000 Luxembourgers are over 65 years of age. In 1983, the full time work force was 158,500 and the unemployment rate was 1.6%. Women comprise about 40% of the labor force. The inflation rate has declined sharply, from 8.6% in 1983 to 5.7% in 1984. A large portion of the average household budget is allocate toward further education, leisure, and culture. About 70% of the population are homeowners. The atmosphere of austerity present elsewhere in Europe has not affected Luxembourg; leaders are optimistic about the country's economic future.^ieng

France. Country profile. [France's economy adjusts to a declining birth rate].

PIP: This discussion of France focuses on regions and cities, age distribution, households and families, housing, labor force, consumption, education, and communications. France counted 54,334,871 citizens as of March 4, 1982. There were 250,000 more people than in 1975, yielding a 7-year growth rate of 3.3%. If present trends continue, there will be 56 million French by the end of the 1980s. Since 1975 when the last census was conducted, cities of more than 200,000 lost an average of 5% of their residents. For the 1st time in more than a century, urban areas of 20,000 or more did not gain population but merely held their own. France continues to experience the effects of the large-scale decimation of its male population during the 2 world wars. The World war i loss showed up March 1982 as a relatively smaller 60-74 group. Conversely the population aged 75 and over is growing, both in absolute numbers and as a percent of the population. There were 3.6 million aged 75 and over (6.6% of the population) in 1982 compared with 3 million (5.6%) in 1975. The 19 and under age group declined between 1975-85, from 31% (16.2 million) to 29% (15.6 million). The 20-59 year old group constitutes the largest segment of the population--about double the group aged 19 and under--and its growing. This group was 50% of the population in 1973 and 53% in 1982. The infant mortality rate has declined steadily in France, from 18.2 deaths/1000 births in 1970 to 13.6 in 1975 and 9.5 at present. The total fertility rate has continued to decline: 1.8 children/woman in the 1982 census a rate less than the number needed to replace the present French population. Between 1975-82 households grew 10.4% to a total of 19.6 million. The growth in the number of households is attributed to the increase in divorce and the tendency for French children to leave the parental home at an earlier age. France has nearly 23 million dwelling places. More than half of householders own their own homes. New housing starts declined markedly since 1975. In 1982 France had 23.5 million economically active people, including 2 million unemployed. Both figures are higher today with at least 10% of the population seeking work. Most French earn less than 8000 francs/month. The average weekly household expenditure in 1981 was 2076 francs, about $460 at 1981 exchange rates. Food took the biggest share at 439 francs. In 1983 France had 13.9 million students enrolled in primary and secondary schools and more than 905,000 in universities. France has an estimated 18.5 million television households and has 104 dailies and 850 weekly and shopper newspapers.^ieng

Republic of Ireland: Ireland moves urban and east.

PIP: This discussion of the Republic of Ireland focuses on regions and cities, vital statistics, households, income and consumption, labor force, education, and information sources. Beginning in 1926, the government of Dublin has taken 10 full or partial censuses, since partition in December 1921 creating the 26-county Irish Free State as part of the British Commonwealth and 6-county Northern Ireland as part of the UK. Data from the 1979 census are sometimes used in official reports, but this profile is based on the last full census taken on the evening of April 5, 1981. The 1981 census counted 3,443,405 people in the Republic (the 1979 population of Northern Ireland was 1,543,300). Of the Republic's total population, 55.6% were in towns compared with 53.2% in 1971. Since the 1971 census the town population increased by 20.8% and nontown population increased by 9.7%. Ireland has shown significant population growth only in the past 10 years. Ireland's overall population density is only 49 people/sq km, compared with the Common Market average of 170 people/sq km. Yet moving east and urban is an unswerving trend in modern Ireland, and more than half the Irish population now live in urban areas. There were 695,000 births in Ireland from 1971-81 and 333,000 deaths. Ireland's infant mortality rate was 11/1000 births, comparable with most Common Market countries. Marriage, birth, and death statistics are not collected in the census but are taken from central registry office records. The average number of children an Irish woman will have in her lifetime (total fertility rate) has declined from about 4 in the mid 1960s to about 3 children in 1980. Whether the fertility decline will continue is questionable. Birth control devices for both men and women cannot be purchased officially without a doctor's prescription in the 94% Roman Catholic Republic. Some doctors and women's groups oppose the legal ban but risk fines and imprisonment. Divorce is an area of Irish life that is changing. The law that prohibits divorce is being challenged in the European Court of Justice by 1 "commonlaw" couple who live together because 1 member cannot legally divorce. The 1981 census estimated 907,800 households, an increase of about 177,000 in the past decade. The traditionally large Irish family is on the decline, dropping from about 3.94 people per household in 1971 to 3.66 people per household. Average weekly industrial earnings in 1979 amounted to little more than 85 sterling, but for 1982 men's average weekly earnings in sterling were 148.66 and women's were 88.63. The 1981 census found 1,150,700 people at work, or about 33% of the population. 29% of those working were women. Of the 335,300 women in the labor force, nearly 64% are single. School attendance is compulsory for children aged 6-15. School enrollment has increased steadily since 1960. To date 3 census documents have been issued by the government printing office.^ieng