Circadian and circannual rhythms of hormonal variables in elderly men and women

A group of fourteen men (73 ± 5 yr of age), and eighteen women (77 ± 7 yr of age) institutionalized at the Berceni Clinical Hospital, Bucharest, Romania, were studied over a 24-hr span once during each season (winter, spring, summer and fall). All subjects followed a diurnal activity pattern with rest at night and ate three meals per day with breakfast at about 0830, lunch at about 1300 and dinner at about 1830. The meals were similar, although not identical for all subjects during all seasons. On each day of sampling blood was collected at 4-hr intervals over a 24-hr span. Seventeen hormonal variables were determined by radioimmunoassay. Statistically significant circadian rhythms were detected and quantitated by population mean cosinor analysis in pooled data from all four seasons in both sexes for ACTH, aldosterone, Cortisol, C-peptide, dehydroepiandrosterone-sulfate (DHEA-S), immunoreactive insulin, prolactin, 17-OH progesterone, testosterone, total T₄ and TSH. In women, estradiol and progesterone also were determined and showed a circadian rhythm during all seasons. Total T, and FSH showed circadian rhythm detection by cosinor analysis in the men only; LH showed no consistent circadian rhythm as group phenomenon in men or women.

A circannual rhythm was detected using the circadian means of each subject at each season as input for the population mean cosinor in the women for ACTH, C-peptide, DHEA-S, FSH, LH, progesterone, 17-OH progesterone and TSH. In the men, a circannual rhythm was detected for ACTH, FSH, insulin, LH, testosterone and T₃. There were phase differences between men and women in ACTH, FSH and LH. In those functions in which both the circadian and circannual rhythms were statistically significant, a comparison of the amplitudes showed in the women a higher circannual rather than circadian amplitude for DHEA-S. In 17-OH progesterone, TSH and C-peptide, the circadian amplitude in women was larger. In men, the circannual amplitude of T₃ was larger than the circadian amplitude and in insulin the circadian amplitude was larger than the circannual amplitude. There was no statistically significant difference between the circadian and circannual amplitudes in the women in ACTH and progesterone and in the men in ACTH and testosterone.     

Circadian and Circannual Rhythms of Hormonal Variables in Elderly Men and Women

A group of fourteen men (73 ± 5 yr of age), and eighteen women (77 ± 7 yr of age) institutionalized at the Berceni Clinical Hospital, Bucharest, Romania, were studied over a 24-hr span once during each season (winter, spring, summer and fall). All subjects followed a diurnal activity pattern with rest at night and ate three meals per day with breakfast at about 0830, lunch at about 1300 and dinner at about 1830. The meals were similar, although not identical for all subjects during all seasons. On each day of sampling blood was collected at 4-hr intervals over a 24-hr span. Seventeen hormonal variables were determined by radioimmunoassay. Statistically significant circadian rhythms were detected and quantitated by population mean cosinor analysis in pooled data from all four seasons in both sexes for ACTH, aldosterone, Cortisol, C-peptide, dehydroepiandrosterone-sulfate (DHEA-S), immunoreactive insulin, prolactin, 17-OH progesterone, testosterone, total T₄ and TSH. In women, estradiol and progesterone also were determined and showed a circadian rhythm during all seasons. Total T, and FSH showed circadian rhythm detection by cosinor analysis in the men only; LH showed no consistent circadian rhythm as group phenomenon in men or women.

A circannual rhythm was detected using the circadian means of each subject at each season as input for the population mean cosinor in the women for ACTH, C-peptide, DHEA-S, FSH, LH, progesterone, 17-OH progesterone and TSH. In the men, a circannual rhythm was detected for ACTH, FSH, insulin, LH, testosterone and T₃. There were phase differences between men and women in ACTH, FSH and LH. In those functions in which both the circadian and circannual rhythms were statistically significant, a comparison of the amplitudes showed in the women a higher circannual rather than circadian amplitude for DHEA-S. In 17-OH progesterone, TSH and C-peptide, the circadian amplitude in women was larger. In men, the circannual amplitude of T₃ was larger than the circadian amplitude and in insulin the circadian amplitude was larger than the circannual amplitude. There was no statistically significant difference between the circadian and circannual amplitudes in the women in ACTH and progesterone and in the men in ACTH and testosterone.     

Chronobiological study of several enzymes of lysosomal origin in human plasma

The possible occurrence of circadian and circannual rhythms in the plasma concentrations of the following enzymes of lysosomal origin was assessed: beta-D-N-acetylglucosaminidase (EC 3.2.1.30) beta-D-glucuronidase (EC 3.2.1.31), beta-D-glucosidase (EC 3.2.1.21), beta-D-galactosidase (EC 3.2.1.22), alpha-D-galactosidase (EC 3.2.1.23), alpha-L-fucosidase (EC 3.2.1) and alpha-D-mannosidase (EC 3.2.1.24). The circadian rhythm was studied in 16 women (aged: 17-24 years) and 13 men (age: 23 years) volunteers; the circannual rhythm, in 10 women and 8 men (age: 20-25 years). The circadian rhythm was detected in all the tested enzymes of women, and only in alpha-D-galactosidase, beta-D-glucosidase, alpha-D-mannosidase and beta-D-acetylglucosaminidase of men. A statistically significant difference between genders in the circadian rhythm was exhibited by beta-D-galactosidase (MESOR; amplitude) beta-D-glucosidase (MESOR; amplitude; acrophase) beta-D-N-acetylglucosaminidase, beta-D-glucuronidase and alpha-D-galactosidase (MESOR) and alpha-L-fucosidase (amplitude, acrophase). A circannual rhythm was detected in all the tested enzymes with the exception of beta-D-glucuronidase and beta-D-N-acetylglucosaminidase; no statistically significant difference between genders was detected. The group rhythms of some of the enzymes (alpha-D-galactosidase, beta-D-glucosidase, beta-D-galactosidase) showed similar values of both circadian and circannual acrophases, suggesting that they may subjected as a group to the same chronobiological coordination, possibly mediated by hormones. The chronobiological rhythms of lysosomal enzymes were different from those of lactate dehydrogenase and alpha 1-antitrypsin, indicating that these rhythms are not merely reflecting fluctuations of the water content of plasma. No in-phase relationship was observed between the circadian and circannual rhythms of plasma cortisol and those of the tested lysosomal enzymes, excluding a direct chronobiological and possibly functional relationship between this hormone and lysosomal enzymes.     

Maternal thyroid function in early and late pregnancy.

Thyroid function was investigated during and after pregnancy in 12 healthy euthyroid women. During pregnancy, serum total T4 (TT4) levels were significantly elevated and nearly stable, while thyroxine-binding globulin (TBG) levels progressively increased till the 7th month. A slight elevation, though not significant, of free T4 (fT4) was recorded in early pregnancy. In the following months, fT4, free T3 (fT3) and the T4/TBG ratio progressively diminished, reaching a plateau at the 7th month. Serum TSH levels, measured by an ultrasensitive immunofluorometric assay, were comparable to postpartum values during the first trimester and showed a moderate upward trend with the progression of pregnancy. The evaluation of 24-hour TSH profiles was performed in 5 women during the first trimester of pregnancy. In all women, the circadian rhythm of TSH was present with a normal nocturnal surge, though anticipated in 1 case. In summary (1) during the first trimester of pregnancy, the increased thyroid activity does not seem to be only sustained by pituitary TSH which remains unmodified; the negative correlation between TSH and hCG levels might suggest that hCG also stimulates the gland to increase thyroid hormone output, and the presence of a normal TSH circadian rhythm indicates that the central mechanism of neuroregulation of the pituitary-thyroid axis is preserved in early pregnancy, and (2) in late pregnancy, a marked decrease in free thyroid hormone fractions is accompanied by serum TSH levels still in the normal range, indicating a modification of thyroid homeostasis which might recognize various etiological factors.     

Relationship between pituitary-thyroid axis hormones and anthropometric parameters in Czech adult population

Although the relationships between thyroid function and anthropometric parameters were studied in patients with thyroid disorders and in morbidly obese subjects, such data in normal healthy population are scarce. In our study, relationships between factors of body composition, fat distribution and age with hormones of the pituitary-thyroid axis were evaluated in a large, randomly selected sample of normal adult Czech population comprising of 1012 men and 1625 women. Our results exhibited weak, but significant relationships between body composition, body fat distribution and the parameters of pituitary-thyroid axis. Some of these associations were gender-specific. As shown by backward stepwise regression model, body fat distribution evaluated by centrality index (subscapular/triceps skinfold ratio) was negatively associated with free triiodothyronine (fT3) serum levels only in women, while a positive correlation of fT3 with BMI was specific for men. BMI was inversely related to free thyroxine (fT4) concentrations in women but not in men. The centrality index (CI) was positively related to TSH levels in both genders. The fT3/fT4 ratio, reflecting deiodinase activity, was inversely related to age and positively related to BMI in both genders, while the highly significant negative correlation between CI and fT3/fT4 ratio was specific for women.     

Oxytocin decreases plasma levels of thyroid-stimulating hormone and thyroid hormones in rats

Oxytocin (OXT) administered to rats induces several long-lasting physiological and metabolic effects. The aim of the present study was to investigate the effects of oxytocin treatment on plasma levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4) and free triiodothyronine (fT3). For this purpose, oxytocin or NaCl was administered intracerebroventricularly (i.c.v.) (0.3 micro g) or subcutaneously (s.c.) (1 mg/kg) once a day for 5 days to male rats. Five or ten days after the last injection, rats were decapitated, blood was collected and hormone levels were analyzed by fluoroimmunoassay. The oxytocin treatment i.c.v. decreased plasma levels of TSH (p<0.05), fT3 (p<0.01) and fT4 (p<0.05) when measured at day 5 after oxytocin treatment, whereas the effect was abolished when measured at day 10. Oxytocin treatment s.c. did not affect plasma levels of TSH, fT3 or fT4. Thus, the effect seems to have been mediated within the central nervous system, and TSH and the thyroid hormones may be involved in some of the metabolic effects in response to oxytocin.     

Age-related changes in plasma dehydroepiandrosterone sulphate, cortisol, testosterone and free testosterone circadian rhythms in adult men

The circadian rhythms of serum luteinizing hormone, follicle-stimulating hormone, testosterone (T), free testosterone (fT), sex hormone-binding globulin (SHBG), oestradiol, cortisol and dehydroepiandrosterone sulphate (DHA-s) have been investigated in 5 normal male adults and 6 elderly men. Circadian rhythms were detected statistically significant (p less than 0.05) by population mean cosinor analysis, for T, fT, cortisol and DHA-s in the young group. In the elderly population, serum cortisol showed a clear circadian rhythm, although with some phase modification, whereas DHA-s secretion lost its circadian rhythmicity. This demonstrates that ageing differently affects the two major adrenal functions, glucocorticoid and androgenic; further, the data suggest that an independent adrenal androgen-regulating system could be selectively impaired in the older subjects. In the elderly group the loss of T circadian rhythm was confirmed, but a statistically significant circadian rhythm of fT was recorded. It was characterized by a marked phase advance and not related with the SHBG modifications found in elderly men. This finding leads us to reconsider the role of fT, which appears more sensitive than total T, in studying circadian rhythm of gonadal androgen secretion.     

Thyroid function, cytokine and IGF-IGFBP interactions in cystic fibrosis patients

BACKGROUND/AIMS: Thyroid function impairment has been sporadically described in cystic fibrosis (CF) and ascribed to iodine overload or selenite deficiency. In this study we evaluated thyroid function in CF in order to verify these data and to evaluate if the modifications were related to serum levels of markers of inflammation and growth factors that we have previously shown to be altered in CF. METHODS: Seventeen young adult CF patients and 18 age-matched controls were enrolled in this study. The diagnosis of CF was confirmed by genetic analysis. None was treated with pulmonary expectorants. Serum IL-1beta, IL-6, TNF-alpha, IGF-I, IGF-II, IGFBP-2, IGFBP-3, TSH, fT3 and fT4 were measured using standard commercial kits. RESULTS: TSH, fT3 and fT4 serum levels were similar in CF patients and controls. Within the patient group, thyroid function did not vary in relation to C-reactive protein serum levels, respiratory function and clinical conditions (Shwachman score). No correlation was found with any growth factor or cytokine analyzed. CONCLUSIONS: At variance with the few previously published data, we did not detect any difference in thyroid function in patients with CF compared with normal healthy subjects. This could be due to the fact that no iodine overload or selenite deficiency was present in our patients. Thyroid function seemed independent of markers of inflammation and IGF-IGFBP serum levels.     

Weight Loss Through Gastric Banding: Effects on TSH and Thyroid Hormones in Obese Subjects With Normal Thyroid Function

Studies on thyroid function in obesity yielded inconsistent results; high thyroid‐stimulating hormone (TSH) levels were generally shown; high free triiodothyronine (fT)‐3 or fT4 levels were described in some, but not in other studies. After weight loss, TSH and thyroid hormones have been described to either increase or decrease. Our aim was to describe TSH, fT3, and fT4 in obese subjects with normal thyroid function before and after durable and significant weight loss, obtained through laparoscopic gastric banding (LAGB), in comparison with nonobese subjects. TSH, fT3, fT4, and fT3/fT4 ratio (an index of D1 and D2 deiodinase activity), were evaluated in 99 healthy controls and in 258 obese subjects, at baseline and 6 months, 1 year, and 2 years after LAGB, together with indexes of glucose (glucose, insulin, homeostasis model assessment of insulin resistance index) and lipid (triglycerides, total and high‐density lipoprotein–cholesterol) metabolism, and anthropometric measures (BMI and waist circumference). Under basal conditions, TSH, fT3, and fT4 were all in the normal range, but higher in obese than in nonobese subjects, and fT3/fT4 ratio was normal; with weight loss, fT3 and fT3/fT4 ratio decreased in obese subjects, while fT4 increased and TSH remained steady; all values were again within the normal range. Albumin and cholesterol levels remained steady, while triglycerides, insulin, and homeostasis model assessment of insulin resistance decreased, and high‐density lipoprotein–cholesterol increased. These changes, however, do not modify TSH, letting us to hypothesize that the changes are due to a decrease of D1 and D2 deiodinase activities.     

Free Thyroxine During Early Pregnancy and Risk for Gestational Diabetes

Several studies have now reported associations between gestational diabetes mellitus (GDM) and low free thyroxine (fT4) during the second and third trimesters, but not in the first trimester. The present study further examines relationships between low fT4, maternal weight, and GDM among women in the FaSTER (First and Second Trimester Evaluation of Risk) trial, in an effort to determine the extent to which thyroid hormones might contribute to causality. The FaSTER cohort includes 9351 singleton, euthyroid women; 272 of these women were subsequently classified as having GDM. Thyrotropin (TSH), fT4, and thyroid antibodies were measured at 11–14 weeks’ gestation (first trimester) and 15–18.9 weeks’ gestation (second trimester). An earlier report of this cohort documented an inverse relationship between fT4 in the second trimester and maternal weight. In the current analysis, women with GDM were significantly older (32 vs. 28 years) and weighed more (75 vs. 64.5 kg). Maternal weight and age (but not TSH) were significantly associated univariately with fT4 (dependent variable), in the order listed. Second trimester fT4 odds ratios (OR) for GDM were 2.06 [95% CI 1.37–3.09] (unadjusted); and 1.89 [95% CI 1.26–2.84] (adjusted). First trimester odds ratios were not significant: OR 1.45 [95%CI 0.97–2.16] (unadjusted) and 1.11 [95% CI 0.74–1.62] (adjusted). The second trimester fT4/GDM relationship thus appeared to strengthen as gestation progressed. In FaSTER, high maternal weight was associated with both low fT4 and a higher GDM rate in the second trimester. Peripheral deiodinase activity is known to increase with high caloric intake (represented by high weight). We speculate that weight-related low fT4 (the metabolically inactive prohormone) is a marker for deiodinase activity, serving as a substrate for conversion of fT4 to free triiodothyronine (fT3), the active hormone responsible for glucose-related metabolic activity.     

Biochemical symptoms of hypothyreosis in the population of Warsaw region

Doctors in Warsaw region claimed that the results of fT4 and TSH examinations originating from different laboratories are incomparable. Therefore the Gaussian Reference Ranges (GRR) of archival sets of data from 6 laboratories (together 18793 fT4 and 44851 TSH results) were calculated separately with JEG method. The upper and lover ranges were compared with data from 11 bibliographical sources. It was found that in the investigated population the both averaged ranges (high and low) of GRR of fT4 are statistical significant lover then the reference data. In the same time the averaged upper range of GRR of TSH was higher than the averaged data from the literature. Based on statistic analysis of these results it could be estimated that about 20% of the investigated population show evident and about 50% show moderate signs of hypothyreosis.     

An almond-enriched diet increases plasma α-tocopherol and improves vascular function but does not affect oxidative stress markers or lipid levels

Abstract

Vascular dysfunction is one of the major causes of cardiovascular (CV) mortality and increases with age. Epidemiological studies suggest that Mediterranean diets and high nut consumption reduce CV disease risk and mortality while increasing plasma α-tocopherol. Therefore, we have investigated whether almond supplementation can improve oxidative stress markers and CV risk factors over 4 weeks in young and middle-aged men.

Healthy middle-aged men (56 ± 5.8 years), healthy young men (22.1 ± 2.9 years) and young men with two or more CV risk factors (27.3 ± 5 years) consumed 50 g almond/day for 4 weeks. A control group maintained habitual diets over the same period.

Plasma α-tocopherol/cholesterol ratios were not different between groups at baseline and were significantly elevated by almond intervention with 50 g almond/day for 4 weeks (p < 0.05). Plasma protein oxidation and nitrite levels were not different between groups whereas, total-, HDL- and LDL-cholesterols and triglycerides were significantly higher in healthy middle-aged and young men with CV risk factors but were not affected by intake. In the almond-consuming groups, flow-mediated dilatation (FMD) improved and systolic blood pressure reduced significantly after 50 g almonds/day for 4 weeks, but diastolic blood pressure reduced only in healthy men.

In conclusion, a short-term almond-enriched diet can increase plasma α-tocopherol and improve vascular function in asymptomatic healthy men aged between 20 and 70 years without any effect on plasma lipids or markers of oxidative stress.     

TRH test in patients with diabetes mellitus type 1 and/or autoimmune thyroiditis. Changes in the pituitary-thyroid axis, reverse T3, prolactin and growth hormone levels

The response of the pituitary- thyroid axis, reverse triiodothyronine (rT3), prolactin, and growth hormone (GH) levels following TRH stimulus (Relefact TRH 200 microg 2 amp. i.v.) was examined in patients with autoimmune diabetes type 1 (DM1, n=30), with autoimmune thyroiditis (AT, n=25), and with concurrent DM1 and AT (n=22) to evaluate the influence of DM1 and AT of autoimmune pathogenesis on the above-mentioned hormonal parameters. Statistical analysis (ANOVA) showed that: a) the response of TSH did not differ from control groups (C); b) free triiodothyronine (fT3), free thyroxine (fT4) and their ratio in DM1, DM1+AT and C rose in 120 and 180 min, while a similar increase was not seen in AT (p<0.000001); c) rT3 was not present in any group, with rT3 levels higher in AT (p<0.00002) and lower in DM1 (p<0.02); d) the response of GH had a paradoxical character in some patients in all groups, most often in DM1 (52 %, DM1 vs C, p <0.01). The characteristic response difference was not in the peak GH level, but the delayed return to basal levels in DM1 (p<0.0001) and an abrupt one in AT (p<0.0001). The major findings in DM1 were the differences in GH response, while significant impairment of pituitary-thyroid axis and PRL response to TRH was absent. AT was associated with impairment of TRH stimulated fT3, fT4, fT3/fT4 response and changes in rT3 levels, in spite of preserved TRH-stimulated TSH secretion. GH response in AT patients was also altered.     

The morphofunctional characteristics of the neurons in the sensorimotor cortex of old rabbits during the trace assimilation of rhythm]

Extracellular neuronal activity was recorded from 460 neurons from alert young (5-7 months), middle-aged (54-65 months) and old (66-85 months) rabbits. Trace rhythmic activity of sensorimotor cortical neurons was examined after long-lasting (10-20 min) rhythmic (0.5-2 Hz) electrocutaneous stimulation of the contralateral forelimb. Spectral analysis of spike activity showed age-related differences in capability of producing a rhythm of previous stimulation in spontaneous neuronal activity. In young animals propriate rhythmic fluctuations of firing rate appeared after the first or second sessions of stimulations (on the first experimental day), in middle-aged ones--after 2-4 sessions (on the second or third days); cortical neurons in old rabbits did not exhibit trace rhythmic activity. Significant morphological changes in glial and neuronal cells were observed in sensorimotor cortex of old rabbits. It is proposed that morphological deteriorations may be the reason of the impairement of trace processes during aging.     

Aerobic exercise training reduces plasma endothelin-1 concentration in older women.

Endothelial function deteriorates with aging. On the other hand, exercise training improves the function of vascular endothelial cells. Endothelin-1 (ET-1), which is produced by vascular endothelial cells, has potent constrictor and proliferative activity in vascular smooth muscle cells and, therefore, has been implicated in regulation of vascular tonus and progression of atherosclerosis. We previously reported significantly higher plasma ET-1 concentration in middle-aged than in young humans, and recently we showed that plasma ET-1 concentration was significantly decreased by aerobic exercise training in healthy young humans. We hypothesized that plasma ET-1 concentration increases with age, even in healthy adults, and that lifestyle modification (i.e., exercise) can reduce plasma ET-1 concentration in previously sedentary older adults. We measured plasma ET-1 concentration in healthy young women (21-28 yr old), healthy middle-aged women (31-47 yr old), and healthy older women (61-69 yr old). The plasma level of ET-1 significantly increased with aging (1.02 +/- 0.08, 1.33 +/- 0.11, and 2.90 +/- 0.20 pg/ml in young, middle-aged, and older women, respectively). Thus plasma ET-1 concentration was markedly higher in healthy older women than in healthy young or middle-aged women (by approximately 3- and 2-fold, respectively). In healthy older women, we also measured plasma ET-1 concentration after 3 mo of aerobic exercise (cycling on a leg ergometer at 80% of ventilatory threshold for 30 min, 5 days/wk). Regular exercise significantly decreased plasma ET-1 concentration in the healthy older women (2.22 +/- 0.16 pg/ml, P < 0.01) and also significantly reduced their blood pressure. The present study suggests that regular aerobic-endurance exercise reduces plasma ET-1 concentration in older humans, and this reduction in plasma ET-1 concentration may have beneficial effects on the cardiovascular system (i.e., prevention of progression of hypertension and/or atherosclerosis by endogenous ET-1).     

Circadian and circannual study of the hypophyseal-gonadal axis in healthy young males

Circadian and circannual variations of Testosterone, FSH and LH secretions, other than Oral Body Temperature (OBT) have been studied in four healthy males. OBT showed a constant circadian rhythm with an acrophase located in the afternoon. Plasma Testosterone exhibited both a circadian (acrophase = hr 09,28) and a circannual rhythm (acrophase = 22 february); plasma FSH also showed a circannual rhythm (acrophase = 13 february). By mean chronogram +/- SEM we documented the highest LH levels in December and the lowest in February. These observations would suggest the hypothesis that the winter could be the period in which the hypophysis-gonadal axis in young males exhibits its maximal activity as previously documented for other hormones.     

Diurnal and seasonal changes in semen quality of men in subfertile partnerships

ABSTRACT

Circadian and circannual rhythms influence not only the environment, but also human physiology. In times of increasing numbers of couples struggling with infertility, and thus increasing demand for successful assisted reproduction, the aim of our study was to evaluate circadian and circannual rhythms and their association with semen quality. A total of 12 245 semen samples from 7068 men, collected at the andrology laboratory of the Department of Reproductive Endocrinology, University Hospital Zurich, between 1994 and 2015, were uniformly analysed in terms of sperm concentration, total sperm count, progressive motility and normal morphology. On the basis of these four parameters, we retrospectively examined the circadian and circannual changes of semen quality. The Mann–Whitney U test and multiple linear regression analysis were used for the statistical evaluation. The semen samples collected in the early morning before 7:30 a.m. showed the highest levels in sperm concentration, total sperm count and normal morphology, all with statistical significance. Progressive motility did not show any significant alterations based on circadian rhythm. Furthermore, a significant increase in sperm concentration and total sperm count was found in spring, with significant decreases in the summer. The highest percentage of normal morphology was found in summer. For progressive motility, no significant seasonal variation could be demonstrated. Male semen quality varies with both circadian and circannual rhythms. Collection of semen in the early morning, where semen quality was highest, can be used to improve natural fertility as well as fertility resulting from assisted reproduction.     

Effects of exogenous testosterone on testicular luteinizing hormone and follicle-stimulating hormone receptors during aging

During aging, the male Japanese quail exhibits a loss of fertility, increased morphological abnormalities in the testes, and a higher incidence of Sertoli cell tumors. Although there is a coincident loss of reproductive behavior, plasma androgen levels remain high until testicular regression occurs in association with senescence. The purpose of this study was to compare mean specific binding of chicken luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as a measure of testicular receptors during identified stages during aging. Males were categorized according to age (young = 9 months, middle aged = 24 months, or old = 36+ months) and sexual behavior (active or inactive). Testicular samples were collected immediately after perfusion with 4% paraformaldehyde from the following groups: young active (n = 8), young photoregressed (n = 5), young photoregressed plus testosterone implant (n = 4), middle-aged active (n = 8), middle-aged inactive (n = 4), old inactive (n = 5), and old inactive plus testosterone implant (n = 6). A crude plasma membrane fraction was prepared from the testes of each bird and an aliquot deriving from 10 mg of testicular tissue was used for binding assay. Specific binding of labeled LH or FSH was expressed as percentage of total radioactive hormone. Results showed significant (P < 0.05) age-related decreases in both FSH and LH receptor numbers. The highest FSH binding was found in young and middle-aged active males, with low binding in old inactive males. Testicular LH binding decreased during aging, with a sharp decrease in middle-aged males, which was similar to old males. Testosterone implants weakly stimulated FSH and LH binding in old males. Both LH and FSH binding decreased in photoregressed young males. However, testosterone implants stimulated increased LH binding, but did not affect FSH binding in young photoregressed males. These results provide evidence for separate regulation of testicular LH and FSH receptors, with testosterone stimulation of LH receptor, but not FSH receptor number in young males. However, during aging there appears to be a loss of this response, potentially because of the reduced efficacy of testosterone stimulation, thereby implying a diminished capacity for response with aging.     

Chronobiologic quantification of nocturnal low-dose dopamine effect on circadian rhythms of thyroid-related hormones and prolactin (PRL)

Six clinically-healthy young men provided plasma samples every 30 min for 24 h (from 09:00-09:00 on 2 occasions. TSH, free T3 and free T4 were determined in the 30-min samples, while prolactin was determined in samples 1-3h apart. During the first test span, each man received an infusion of physiologic saline between 21(00)-01(00). Upon re-sampling several weeks later, 3 men received a low dose of dopamine (0.1 microgram/kg/min) and 3 men received a high dose (1.0 microgram) over the same hours (21:00-01:00). The least-squares fit of a 24-h cosine to each data series described a statistically-significant circadian rhythm (p less than 0.01) for each subject on each day of study. While overall group comparisons revealed no significant difference in mesor for any hormone studied, some intra-individual differences in rhythm parameters between saline and dopamine infusion were found. Dopamine Rx produced a statistically-significant increase in amplitude for PRL and T4 and an advance in acrophase for TSH, T3 and T4, but a delay for PRL. Studies measuring hormones of interest for the 24th immediately preceding and the 24th immediately following dopamine infusion at varying circadian stages (rather than only between 21:00-01:00) are warranted and have to be individualized--one of the points of this paper. The other main point is that data reduction to a mean and a standard deviation entails loss of information that can be recovered by chronobiologic methods, here used only as a model, in view of the limitations of the sampling design on hand.     

Aging and gender affect the response of thyrotropin (TSH) to gastrin releasing peptide (GRP) in rats

We had previously shown that GRP acts directly at the pituitary gland inhibiting basal and TRH-stimulated TSH secretion in adult male rats. In this study we showed a gender dimorphism in this response of old animals pituitaries to GRP. In both female and male young adult animals, GRP-incubated pituitaries showed approximately 50% less basal and TRH-stimulated TSH secretion to the medium, without affecting the pituitary content of TSH. However, GRP did not have any significant effect upon TSH secretion in old male rats, but the old female showed the same degree of response to GRP as the young adult female rat, regarding basal and TRH-stimulated TSH secretion, while the TSH pituitary content after GRP incubation was higher than that of the young female group. Our data suggest a loss of thyrotrope responsiveness to GRP in aged male rats that could contribute to the decrease in TSH pituitary stores leading to lower basal and TRH-stimulated TSH secretion. Meanwhile, the preservation of GRP responsiveness could help in the relative maintenance of these parameters in the old female rat.