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PubMed2001

Does leptin modulate immune and endocrine response in the time of LPS-induced acute inflammation?

OBJECTIVES: In many studies it has been reported, that leptin may play an important role not only in the regulation of food intake and body weight but can modify immune response. The aim of our study was to estimate the effects of the administration of exogenous leptin on serum concentration of proinflammatory cytokines (interleukin 6-IL 6 and tumor necrosis factor alpha-TNF alpha) and anti-inflammatory cytokine (interleukin 10 - IL 10) during LPS induced acute inflammation. We also estimated leptin's influence on pituitary, thyroid, adrenal and gonadal hormones in response to lipopolysaccharide (LPS) induced acute inflammation. METHODS: Male rats Wistar-Kyoto were divided into four groups, which received respectively: placebo (0.9% NaCl), LPS, leptin and leptin with LPS. The TNF alpha and IL 6 serum concentrations were measured after 2 hours and IL 10 after 4 hours. The pituitary, thyroid, adrenal and gonadal hormones serum concentrations were measured after 2 and 4 hours. Cytokine concentrations were estimated using ELISA tests and hormones concentrations using RIA tests. RESULTS: Leptin did not have an effect on both cytokine responses (proinflammatory and anti-inflammatory) in the time of LPS-induced acute inflammation. Leptin enhanced LPS-induced increasing of corticosterone secretion after 2 hours and decreased LPS-induced inhibition of testosterone secretion after 4 hours. CONCLUSIONS: Leptin can modulate hormone response during LPS-induced acute inflammation.

Animals↗
PubMed1997

Effect of inhibition of increased gonadotrophin secretion before 20 weeks of age in bull calves on testicular development.

In bull calves serum concentrations of LH, FSH, and to a lesser extent testosterone, are increased transiently, between 6 and 20 weeks of age. The function of gonadotrophin and testosterone secretion in this period of growth and development was tested by injecting five Hereford bull calves with a GnRH agonist (15 mg Leuprolide acetate) i.m. at 6, 10 and 14 weeks of age; five vehicle treated calves acted as controls. On the basis of blood samples taken every 15 min for 10 h, at 12 weeks of age, mean serum concentrations of LH, FSH and testosterone and LH and FSH pulse frequency and amplitude were decreased (P < 0.05) by Leuprolide acetate. At 24 weeks of age, mean serum concentrations of LH, and LH and FSH pulse frequency in Leuprolide acetate treated calves exceeded (P < 0.05) that seen in control calves. On the basis of blood samples taken every other week, treatment with Leuprolide acetate decreased mean serum concentrations of FSH and testosterone at 14, 16 and 18 weeks of age compared with control calves and delayed the peak of the early increase in LH secretion from 20 to 24 weeks of age (P < 0.05). Scrotal circumference between 22 and 50 weeks of age, pixel units from ultrasound images of the testes, testis mass at castration at 50 weeks of age, and numbers of spermatids and pachytene spermatocytes were all lower in Leuprolide treated calves than in controls. A transient increase in secretion of LH, FSH and testosterone in young bull calves before 20 weeks of age may, therefore, be a critical step in the initiation and timing of testicular development in bull calves.

Animals↗
PubMed1978

Recent advances in the pharmacologic regulation of fertility in men.

An updated review of research into contraceptives for men is presented. New concepts of the pharmacologic effects of chemical agents on germinal stem cells and spermatogenic arrest, and the effect of new compounds that act at the post-testicular level but do not affect androgen production are discussed. The latest results of studies on steroidal compounds that inhibit pituitary secretion of gonadotropin and hence result in suppression of spermatogenesis and testosterone secretion are presented. The newer contraceptive pills for men are also evaluated. The major drawback to the development of chemical contraceptives for men is the fear of genetic damage and impotence. New and continued research into this type of contraception is urgently needed.

Alkylating Agents↗
PubMed1992

[In vivo and in vitro effects of GnRH analogs on ovarian Leydig cell tumor].

A 65-year old patient, suspected to be suffering from an androgen producing ovarian tumour, was treated preoperatively with the GnRH agonist triptorelin (500 micrograms/day s.c.) for 7 days. After an initial rise, gonadotrophin levels were suppressed under this treatment. The elevated serum testosterone concentrations were reduced by approx. 50% by the triptorelin injections. After the extirpation of the tumour (histologically a Leydig cell tumour of the ovary without signs of malignancy), primary cell cultures which secreted testosterone and androstenedione were prepared. Coincubation of the tumour cells with the GnRH agonist triptorelin had no effect on their androgen secretion. Treatment of the tumour cells with high concentrations (10(-5) M) of a GnRH antagonist, however, resulted in a 100% increase of their testosterone and androstenedione secretion. GnRH-binding sites of low affinity (Ka = 0.54 x 10(5) M-1) and high capacity (B max = 1364 x 10(-12) M/mg membrane protein) were identified in the tumour. These findings suggest that GnRH analogues might modify androgen secretion of sex-cord stromal tumours of the ovary via the suppression of endogenous gonadotrophin secretion and possibly also via direct effects on the tumour cells.

Aged↗
PubMed1998

Therapeutic role of androgens in the treatment of osteoporosis in men.

There has been much recent interest in the relationship between androgens and bone mineralization in men. Increases in serum androgens during puberty allow for skeletal maturation and the attainment of peak bone mass, and the persistence of normal testosterone secretion during adulthood is important for the maintenance of bone density. Testosterone deficiency is associated with heightened bone turnover and is a major risk factor for osteoporosis in men. The administration of testosterone to androgen-deficient men leads to an increase in bone mass, particularly in the trabecular bone compartment, and a reduction in levels of surrogate markers of bone turnover, suggesting that androgens have a dampening effect on bone remodelling. In addition, the administration of androgens to eugonadal men with idiopathic osteoporosis, with resulting supraphysiological testosterone concentrations, may lead to increases in bone mineral density. The risk of osteopenia due to androgen deficiency and the benefits of testosterone substitution therapy or supraphysiological administration on bone will be reviewed.

Adult↗
PubMed2001

Loss of gender difference in serum leptin levels and its slow recovery after successful surgery for Leydig cell tumours in two virilized females.

One of the factors that predicts serum leptin levels is gender. It has been shown that sex steroid hormones, in particular testosterone, play an important role in the regulation of serum leptin levels. We had the opportunity to examine the effects of acute and chronic changes in serum testosterone levels on serum leptin concentrations in two virilized females harbouring testosterone-secreting ovarian tumours, before and after curative surgery. Chronically elevated basal testosterone levels (46 nmol/l) were associated with suppressed serum leptin levels (1.46 microg/l and 2.56 microg/l) vs. 12 age- and BMI-matched healthy subjects 9.89 +/- 0.64 microg/l. Leptin levels were determined from pooled serum samples assayed by commercial radioimmunoassay. High testosterone levels abolished the well known sexual dimorphism of serum leptin levels. Two weeks after curative resection of these tumours serum leptin levels were unaltered and started to increase progressively after one month. One patient received parenteral conjugated oestrogens while the other resumed spontaneous menstrual cycles. Three months after curative surgery obvious changes in body composition were registered (DEXA). Six months later further rise in serum leptin concentrations occurred without further changes in body composition. In conclusion, leptin levels did not change in spite of rapid changes in the steroid milieu, but in the long term increase in body fat stores, new steroid milieu and maybe other factors are important determining factors of serum leptin levels.

Adult↗
PubMed2004

Social condition affects hormone secretion and exploratory behavior in rats.

Studies of behavior, endocrinology and physiology have described experiments in which animals housed in groups or in isolation were normally tested individually. The isolation of the animal from its group for testing is perhaps the most common situation used today in experimental procedures, i.e., there is no consideration of the acute stress which occurs when the animal is submitted to a situation different from that it is normally accustomed to, i.e., group living. In the present study, we used 90 male 120-day-old rats (Rattus norvegicus) divided into 5 groups of 18 animals, which were housed 3 per cage, in a total of 6 cages. The animals were tested individually or with their groups for exploratory behavior. Hormones were determined by radioimmunoassay using specific kits. The results showed statistically significant differences between testing conditions in terms of behavior and of adrenocorticotrophic hormone (ACTH: from 116.8 +/- 15.27 to 88.77 +/- 18.74 when in group and to 159.6 +/- 11.53 pg/ml when isolated), corticosterone (from 561.01 +/- 77.04 to 1036.47 +/- 79.81 when in group and to 784.71 +/- 55.88 ng/ml when isolated), luteinizing hormone (from 0.84 +/- 0.09 to 0.58 +/- 0.05 when in group and to 0.52 +/- 0.06 ng/ml when isolated) and prolactin (from 5.18 +/- 0.33 to 9.37 +/- 0.96 when in group and to 10.18 +/- 1.23 ng/ml when isolated) secretion, but not in terms of follicle-stimulating hormone or testosterone secretion. The most important feature observed was that in each cage there was one animal with higher ACTH levels than the other two; furthermore, the exploratory behavior of this animal was different, indicating the occurrence of almost constant higher vigilance in this animal (latency to leave the den in group: 99.17 +/- 34.95 and isolated: 675.3 +/- 145.3 s). The data indicate that in each group there is an animal in a peculiar situation and its behavior can be detected by ACTH determination in addition to behavioral performance.

Adrenocorticotropic Hormone↗
PubMed1984

Gonadotropin and steroid secretory patterns during chronic treatment with a luteinizing hormone-releasing hormone agonist analog in men.

LHRH agonist analogs induce hypogonadism in man but the mechanism is uncertain. To evaluate this, we treated 13 normal men with 50 micrograms/day D-Trp6,Pro9-NEt LHRH (LHRHA) for periods up to 8 weeks and measured (1) patterns of endogenous gonadotropin and testosterone secretion, (2) gonadal response to exogenous human LH infusions, and (3) gonadotropin and testosterone responses to hourly bolus doses of LHRH. Seven men were evaluated with frequent sampling for 12-h periods every 4 week during treatment with LHRHA. Before treatment, all had three to four spikes of LH in 12 h. On the first day of treatment, the response to LHRHA was tested in four of the men, and there were significant increases in LH, FSH, and testosterone. After 4 weeks, all men had dramatic decreases in mean testosterone levels and blunted or absent gonadotropin responses to acute injection of LHRHA. Mean gonadotropin levels at 4 and 8 weeks were variable; values lower than pretreatment basal levels were found in three men, while unchanged or higher values were found in the remaining four. The pulsatile pattern of LH secretion, characteristic among these men before treatment, was lost during LHRHA therapy. Forty-eight-hour constant infusion of human LH in four other analog-treated men resulted in increases in serum testosterone comparable to those in untreated men. Pulsatile administration of native sequence LHRH to two other men during chronic treatment with LHRHA failed to elicit demonstrable responses in serum gonadotropin or testosterone levels. LHRHA produced a qualitative change in the pattern of LH release from the pituitary. Mean basal LH levels varied during treatment, but the normal pulsatile pattern was diminished. The gonadotropin response to pulsatile administration of LHRH was lost during chronic treatment with LHRHA, but the Leydig cell remained responsive to exogenous human LH. Thus, the locus of action of the analog appears to be at the level of the pituitary in man.

Adult↗
PubMed1991

Immunoneutralization of inhibin modifies hormone secretion and sperm production in bulls.

The objective of this study was to examine the role of endogenous inhibin in the regulation of FSH, LH, and testosterone secretion and sperm production in bulls. Bulls were actively immunized against bovine inhibin alpha 1-26 gly-tyr (bINH) conjugated to human alpha globulin (HAG) or HAG alone (controls) and emulsified in Freund's complete adjuvant. Primary immunization was at 14 wk of age, followed by booster immunizations in Freund's incomplete adjuvant at 28, 30, and 34 wk of age. Ten days after each booster immunization, scrotal circumferences and body weights were measured, and blood was sampled for determination of bINH antibody titer. Ten days after the third booster, blood was sampled at 1-h intervals for 8 h to quantify serum concentrations of FSH, LH, and testosterone. After this blood sampling period, bulls were castrated and testicular sperm production was determined. Serum diluted 1:4,000 from bINH-immunized bulls bound 36%, 52%, and 53% of radioiodinated bINH after the first, second, and third boosters, respectively. Serum from controls bound less than 1% radioiodinated bINH. After the third booster, serum concentrations of FSH and testosterone were increased (p less than 0.05) and LH concentrations were decreased (p less than 0.001) in bINH-immunized bulls compared with controls. After the third booster, daily sperm production per gram of testicular parenchyma was increased (p less than 0.05) in bINH-immunized bulls compared with controls. Scrotal circumferences and body weights were similar between treatment groups throughout the experiment. We concluded that inhibin has a role in regulation of secretion of gonadotrophins and testosterone and testicular sperm production, but not testicular growth, in bulls.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-Globulins↗
PubMed1975

A model of the endocrine regulation of the female reproductive organs.

A biocybernetical analysis was accomplished for a better understanding of the hormonal management in breast cancer therapy, which is based on reported experimental facts and observations. By this a graphentheoretical model of regulation could be obtained answering some unsolved questions. These questions concern the hypothalamic control of the LTH secretion, the regression of the reproductive organs, the significance of that cyclic testosterone secretion by the ovaries recently reported, and the importance of HCG in the establishment of pregnancy and in proliferation of mammary tissue.

Breast Neoplasms↗
PubMed1988

Short-term pituitary-testicular responses of prepubertal ram lambs to hemicastration.

To examine the short-term effects of hemicastration on pituitary-gonadal responses, 12 ram lambs were anesthetized and hemicastrated at 4 mo of age and killed (n = 4) at 2 (HC2), 7 (HC7), or 14 (HC14) days following surgery. Four intact (INT) rams were killed 14 days following anesthesia. Testis and pituitary weights were similar between HC and INT rams. Serum follicle-stimulating hormone (FSH) in HC rams increased within 6 h, peaked at 12 h, and remained elevated above INT levels throughout the study. Overall mean serum testosterone levels in HC rams were lower than in INT rams for the first 48 h, but were similar by 3 days post-surgery. Pulsatile luteinizing hormone (LH) and testosterone secretion was suppressed for the first 9.5 h following anesthesia and/or surgery in both HC and INT animals. A single LH pulse and succeeding testosterone pulse occurred in 10/12 HC and 4/4 INT rams between 10 and 14 h post-surgery, both of which were lower in amplitude in HC than INT animals. However, on Day 7, pulsatile secretory patterns of LH and testosterone were similar, suggesting compensatory androgen secretion had occurred in HC rams. Pituitary LH content was unaffected by hemicastration. In contrast, pituitary FSH content was greater in HC7 and HC14 compared to HC2 and INT animals. Pituitary gonadotropin hormone-releasing hormone (GnRH) receptor concentrations were similar in INT, HC7, and HC14 rams, but were slightly reduced in HC2 rams. Neither testicular LH nor FSH receptor concentrations were altered by hemicastration at any time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy.

Administration of replacement doses of testosterone to healthy hypogonadal men and supraphysiological doses to eugonadal men increases muscle size. To determine whether testosterone-induced increase in muscle size is due to muscle fiber hypertrophy, 61 healthy men, 18-35 yr of age, received monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist to suppress endogenous testosterone secretion and weekly injections of 25, 50, 125, 300, or 600 mg testosterone enanthate (TE) for 20 wk. Thigh muscle volume was measured by magnetic resonance imaging (MRI) scan, and muscle biopsies were obtained from vastus lateralis muscle in 39 men before and after 20 wk of combined treatment with GnRH agonist and testosterone. Administration of GnRH agonist plus TE resulted in mean nadir testosterone concentrations of 234, 289, 695, 1,344, and 2,435 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Graded doses of testosterone administration were associated with testosterone dose and concentration-dependent increase in muscle volume measured by MRI (changes in vastus lateralis volume, -4, +7, +15, +32, and +48 ml at 25-, 50-, 125-, 300-, and 600-mg doses, respectively). Changes in cross-sectional areas of both type I and II fibers were dependent on testosterone dose and significantly correlated with total (r = 0.35, and 0.44, P < 0.0001 for type I and II fibers, respectively) and free (r = 0.34 and 0.35, P < 0.005) testosterone concentrations during treatment. The men receiving 300 and 600 mg of TE weekly experienced significant increases from baseline in areas of type I (baseline vs. 20 wk, 3,176 +/- 186 vs. 4,201 +/- 252 microm(2), P < 0.05 at 300-mg dose, and 3,347 +/- 253 vs. 4,984 +/- 374 microm(2), P = 0.006 at 600-mg dose) muscle fibers; the men in the 600-mg group also had significant increments in cross-sectional area of type II (4,060 +/- 401 vs. 5,526 +/- 544 microm(2), P = 0.03) fibers. The relative proportions of type I and type II fibers did not change significantly after treatment in any group. The myonuclear number per fiber increased significantly in men receiving the 300- and 600-mg doses of TE and was significantly correlated with testosterone concentration and muscle fiber cross-sectional area. In conclusion, the increases in muscle volume in healthy eugonadal men treated with graded doses of testosterone are associated with concentration-dependent increases in cross-sectional areas of both type I and type II muscle fibers and myonuclear number. We conclude that the testosterone induced increase in muscle volume is due to muscle fiber hypertrophy.

Adolescent↗
PubMed1982

Clinical, endocrinological, and cytological characterization of two 46, XX males.

In two 46,XX males, 20 and 21 yr of age, gonadotropins, testosterone, and estradiol were measured in serum and compared to those in a control group of four men. In addition, in one subject, androgen metabolism was measured in biopsied skin and cultured skin fibroblasts. In both XX men, a pulsatile pattern of gonadotropin, testosterone, and estradiol release into serum was observed. The levels of the gonadotropins and estradiol were higher and the levels of testosterone were lower in XX men than in normal men. hCG stimulation resulted in a significant increase in testosterone secretion, and LRH administration caused a more prolonged rise in gonadotropin levels in the XX men. The administration of estradiol caused a positive feedback response in the XX men and resulted in a suppression of gonadotropin secretion in the controls. Finally, the formations of C-19 metabolites from testosterone and estrone from androstenedione were found to be in the same range in skin and skin fibroblasts from the XX men as in those from normal men. It can be concluded that 46,XX men have altered hypothalamic-pituitary and gonadal function compared to normal men.

Adult↗
PubMed1999

Risks versus benefits of testosterone therapy in elderly men.

'Andropause', like menopause, has received significant attention in recent years. It results in a variety of symptoms experienced by the elderly. Many of these symptoms are nonspecific and vague. For this reason, many authors have questioned the value of androgen replacement in this population. Also in dispute is the normal cutoff level for testosterone beyond which therapy should be initiated, and whether to measure free or total testosterone. Testosterone levels decline with age, with the lowest level seen in men older than 70 years. This age-related decline in testosterone levels is both central (pituitary) and peripheral (testes) in origin. With aging, there is also a loss of circadian rhythm of testosterone secretion and a rise in sex hormone binding globulin (SHBG) levels. Total testosterone level is the best screening test for patients with suspected hypogonadism. If the total testosterone concentration is low, free testosterone levels should be obtained. Prostate cancer remains an absolute contraindication to androgen therapy. Testosterone replacement results in an improvement in muscle strength and bone mineral density. Similar effects are observed on the haematopoietic system. Data on cognition and lipoprotein profiles are conflicting. Androgen therapy can result in polycythemia and sleep apnoea. These adverse effects can be deleterious in men with compromised cardiac reserve. We recommend that elderly men with symptoms of hypogonadism and a total testosterone level <300 ng/dl should be started on testosterone replacement. This review discusses the pros and cons of testosterone replacement in hypogonadal elderly men and attempts to answer some of the unanswered questions. Furthermore, emphasis is made on the regular follow-up of these patients to prevent the development of therapy-related complications.

Aged↗
PubMed1988

[Hypophyseal-Leydig function in the diabetic].

Experimental diabetes in animals induces marked alterations of gonadal androgenic functions: reduction in testis weight, morphological alterations of Leydig cells, decrease of plasma testosterone levels and reduction of the ability of the Leydig cells to secrete testosterone in vitro. hCG treatment restores the testicular endocrine function; in addition several morphological and functional changes are observed in the hypothalamic-hypophyseal-gonadal axis which are probably responsible for the testicular lesions found in untreated experimental diabetes mellitus. In diabetic men, the hypothalamic-hypophyseal-gonadal axis seems to be normal (with exception of individual cases); Mean plasma levels of testosterone, LH, FSH and the responses of the gonadal axis to hCG and LHRH are normal.

Animals↗
PubMed1988

A possible role for testosterone during luteolysis in the ewe.

Increased peripheral plasma concentrations of testosterone were detected at the commencement of luteolysis and at oestrus in sheep. Daily subcutaneous administration of spironolactone (10 mg kg-1) between days 10 and 16 of the oestrous cycle suppressed testosterone secretion and delayed luteolysis and oestrus. In pregnant ewes no increases in testosterone concentrations occurred between days 10 to 16 after mating and luteal regression, monitored by peripheral progesterone concentrations, was inhibited. It is suggested that aromatisation of testosterone to oestrogens is needed for luteolysis in sheep.

Animals↗
PubMed1982

[Influence of primary hyperprolactinemia on human sexual behavior].

Eighty per cent of men with hyperprolactinaemia are impotent. Sexual deficiency, which for a long time is the only sign of the disease, is partly due to inhibition of testosterone secretion by high prolactin levels but also, probably, to reduced conversion of testosterone to dihydrotestosterone and, perhaps, to a direct effect of prolactin on the neurotransmitters involved in sexual activity. Eighty per cent of women with hyperprolactinaemia have reduced sexual drive and inability to reach orgasm; the underlying mechanisms are as yet unknown. In women, however, the initial symptoms are menstrual disorders. Most sexual disorders in both sexes regress after return to normal of plasma prolactin levels.

Female↗
PubMed1983

The reproductive--endocrine response of adult rams to sexual encounters with estrual ewes is season dependent.

An experiment was conducted with four adult, sexually inexperienced Finnish Landrace rams during the ovine nonbreeding (July) and breeding (October) seasons to determine the influence of components of the rams' mating behavior on the secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and testosterone. On four occasions in both seasons, blood was collected by jugular venipuncture at 20-min intervals during an 8-hr period while rams were (1) separated from, (2) observing with minimal direct physical contact, (3) mounting without intromission, or (4) mating estrous-induced ewes. In comparison with separation periods, mating activity in July was associated with increased mean LH (P less than 0.05) and testosterone levels and number of LH peaks, while in October, obvious increases were detected in only baseline LH levels (P less than 0.05). Circulating LH and testosterone levels either did not change (July) or were depressed (October) during the mounting and observation periods. FSH levels generally remained unaffected by engagement in the various sexual activities. Although a clear relationship between type of sexual activity and mean PRL levels was not observed in July, activities which appeared to involve the most physical exertion tended to be associated with much higher circulating PRL levels in October. These data suggest (1) the act of ejaculation is important in the induction of increases in LH and testosterone secretion that occur in rams in response to mating activity during the nonbreeding season and (2) excessively stressful sexual activities during the breeding season may alter the pattern of secretion of some reproductive hormones.

Animals↗