Rise In Plasma Testosterone Concentrations Research Articles

Birth weight, growth indices, and seminal parameters in male offspring are resilient features to maternal pre-conceptional dietary manipulation in sheep

Gestational diet manipulation can lead to inadequate fetal nutrient supply resulting in low birth weight, limited postnatal growth, and consequently, reduced reproductive performance in the progeny. However, effects of short-term maternal pre-conceptional dietary manipulation on postnatal growth and reproductive parameters of male offspring in large animals remains unexplored. To determine these consequences, female crossbred (Polypay x Dorset) sheep were allocated to three groups (n = 33/group) of dietary manipulation for 21 days prior to mating under the following conditions: (1) control at 100 % of maintenance energy requirements (40 Kcal of metabolizable energy/kg body weight [BW]), (2) undernutrition (UN) at 50 % of Control intake, and (3) overnutrition (ON) at 200 % of maintenance energy. Singleton ram lambs (UN:9; C:12; ON:6) were monitored from birth until 8 months of age, including birth weight, weekly weights, weight gain, body mass index (BMI), and circulating testosterone. After weaning, monthly scrotal circumference and subcutaneous fat depth were measured. Semen morphology and motility were evaluated at 7 and 8 months of age. Birth weight, weight gain, and BMI at birth and weaning were not significantly different among nutritional treatments. None of the pre-conceptional diets affected body weight change from weaning until 36 weeks of age, BMI, fat depth, or scrotal circumference across the experiment. A sustained rise in plasma testosterone concentrations was detected when ram lambs were, on average, 82 days old and 37 kg. Both testosterone concentrations and scrotal circumference were positively correlated to body weight regardless of treatment group. In addition, seminal parameters did not differ among treatments, but a transient increase in plasma testosterone at 18 weeks of age was observed in ON ram lambs compared to control rams. In conclusion, birth weight, growth indices, and seminal parameters in singleton rams are resilient features in the progeny upon maternal pre-conceptional dietary manipulation in sheep.

Gonadotropin-Inhibitory Hormone Inhibits Gonadal Development and Maintenance by Decreasing Gonadotropin Synthesis and Release in Male Quail

Until recently, any neuropeptide that directly inhibits gonadotropin secretion had not been identified. We recently identified a novel hypothalamic dodecapeptide that directly inhibits gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). The action of GnIH on the inhibition of gonadotropin release is mediated by a novel G protein-coupled receptor in the quail pituitary. This new gonadotropin inhibitory system is considered to be a widespread property of birds and provides us with an unprecedented opportunity to study the regulation of avian reproduction from an entirely novel standpoint. To understand the physiological role(s) of GnIH in avian reproduction, we investigated GnIH actions on gonadal development and maintenance in male quail. Continuous administration of GnIH to mature birds via osmotic pumps for 2 wk decreased the expressions of gonadotropin common alpha and LHbeta subunit mRNAs in a dose-dependent manner. Plasma LH and testosterone concentrations were also decreased dose dependently. Furthermore, administration of GnIH to mature birds induced testicular apoptosis and decreased spermatogenic activity in the testis. In immature birds, daily administration of GnIH for 2 wk suppressed normal testicular growth and rise in plasma testosterone concentrations. An inhibition of juvenile molt also occurred after GnIH administration. These results indicate that GnIH inhibits gonadal development and maintenance through the decrease in gonadotropin synthesis and release. GnIH may explain the phenomenon of photoperiod-induced gonadal regression before an observable decline in hypothalamic GnRH in quail. To our knowledge, GnIH is the first identified hypothalamic neuropeptide inhibiting reproductive function in any vertebrate class.

Pituitary and gonadal responses to the long-term pulsatile administration of gonadotrophin-releasing hormone in fetal sheep.

The fetal hypothalamo-pituitary-gonadal axis reaches a peak in activity at mid-gestation and this is followed by a period of suppression which persists until the onset of puberty. The decline in gonadotrophic activity during late gestation is thought to reflect the maturation of central and peripheral feedback signals. In order to establish if sustained pituitary responsiveness is rate limiting to the reinstatement of reproductive function, we have examined the endocrine consequences of repeated pulsatile GnRH administration to male and fetal sheep during late gestation. Beginning on day 121 of gestation (term = 145 days) chronically catheterized fetal sheep were given i.v. pulses of either 500 ng GnRH or saline every 2 h for 14 days. Pituitary and gonadal responses were assessed by measuring changes in plasma concentrations of LH, FSH, inhibin and testosterone (in male fetuses) in response to the first pulse of GnRH on day 1 and to the corresponding pulse on days 4, 7, 10 and 14. In response to the first pulse of GnRH there was an immediate release of LH, with the peak response being significantly (P < 0.01) greater than on subsequent days. In male fetuses each pulse of LH was followed by a rise in plasma testosterone concentrations within 40-60 min. The amplitude of these testosterone responses increased significantly (P < 0.01) after 9 days of treatment despite a decline in the plasma LH response. Basal FSH concentrations increased progressively (P < 0.05) during pituitary stimulation with GnRH in both male and female fetuses. Immunoreactive inhibin concentrations were significantly (P < 0.05) higher in males than in females, and there was a gradual increase throughout the experimental period irrespective of treatment. We observed no inverse correlation between inhibin and FSH concentrations. These data show that pulsatile administration of GnRH to fetal sheep during late gestation results in sustained re-activation of pituitary-gonadal function. The decline in fetal gonadotrophins, which is a characteristic feature of late gestation, is therefore likely to result from inadequate GnRH secretion from the fetal hypothalamus rather than an inhibition of pituitary function by peripheral feedback signals.

Effect of competition stress on tests used to assess testosterone administration in athletes.

The drug test for exogenous administration of testosterone is based on the testosterone/epitestosterone ratio (T/E) in urine. Physiological and psychological stresses may alter plasma testosterone concentrations. The question is to know how much the psychological conditions of competition can modify the T/E ratio. In order to study this issue, 20 athletes practising modern pentathlon participated in a study designed to determine the effects of a pistol shooting trial on their hormonal response. Pistol shooting induces a high psychological stress without increasing energy expenditure. Venous blood samples were drawn before and after the trial according to the usual drug testing procedure. Athletes were separated into two groups: a group of young athletes (n = 10; mean age 19 +/- 0.3 years) and another group of aged subjects (n = 10; mean age 45 +/- 1.5 years). The rise in plasma testosterone concentrations reached 75% in older subjects versus 55% in younger ones. The plasma luteinizing hormone (LH) concentrations were not influenced by the trial. After shooting trial the elevation in cortisol concentrations was greater for older subjects than for younger ones (273 +/- 30 ng.ml-1 vs 173 +/- 7 ng.ml-1). The catecholamine response was identical in both groups. The urinary T/E ratio remained unchanged after the shooting trial and always remained lower than the International Olympic Committee limit of 6. These results indicate that the psychological stress associated with competition increases the production of steroid hormones (testosterone, cortisol), and that this phenomenon is more pronounced in older athletes. These hormonal changes do not influence the urinary excretion of steroid metabolites used as criterion for drug testing.

Gonadotropin-releasing hormone antagonist for postpartum contraception: outcome for the mother and male offspring in the marmoset.

GnRH antagonists have potential for use in postpartum contraception, as it is likely that they would be effective in maintaining the inhibition of ovulation associated with lactation, but possible effects on the infant by transfer of antagonist via breast milk are unknown. The aim of this study was to establish whether chronic treatment with a GnRH antagonist would prevent ovulation throughout the period of lactation using the marmoset monkey as a model and to evaluate the effects of the presence of GnRH antagonist in breast milk on the postnatal rise in plasma testosterone concentrations in male infants. Mothers who had delivered male twins were selected. Starting within 3 days postpartum, mothers (n = 5/group) were treated with either 6.0 or 0.6 mg/kg of the GnRH antagonist antide, sc, once per week for 11 weeks. Ten postpartum lactating females acted as controls. All animals were housed in family groups with fertile males. To determine possible effects on the postnatal rise in testosterone, plasma samples were collected from the male infants of the high dose antide-treated mothers at weekly intervals for 12 weeks. Plasma progesterone concentrations were monitored in lactating mothers until establishment of pregnancy in both treated and control groups. Concentrations of antide were determined by RIA in plasma from mothers in the high dose group, in their milk, and in pooled plasma samples from their infants. Ovulation followed by pregnancy occurred in all of the control animals. No ovulations occurred during treatment with antide. Antide was present throughout treatment in plasma and breast milk in the mother. In male infants feeding from mothers receiving high dose treatment, antide was not detectable in infant plasma, and plasma testosterone concentrations were within the normal range for male neonates in our colony. These results indicate that the GnRH antagonist has potential as a method of contraception postpartum without affecting the postnatal rise in testosterone in male infants.

GnRH in the male dog: dose-response relationships with LH and testosterone.

Dose-response relationships between GnRH and LH, and between GnRH and testosterone, were investigated in six male dogs by intravenous administration of a GnRH analogue at different doses. Each dose of GnRH analogue induced an immediate rise in the plasma concentration of LH and then a rise in plasma testosterone concentration. Irrespective of the dose used, the rise in testosterone began 10 min after the GnRH injection. Administration of GnRH at doses of 0.01, 0.1, 1, 10 and 100 micrograms kg-1 resulted in maximum LH concentrations in plasma (mean +/- SEM; n = 6) of 22 +/- 7, 27 +/- 6, 40 +/- 7, 57 +/- 13 and 56 +/- 10 micrograms l-1, respectively. These doses induced maximum concentrations of testosterone in plasma (mean +/- SEM; n = 6) of 16 +/- 4, 20 +/- 4, 22 +/- 3, 22 +/- 4 and 24 +/- 7 nmol l-1, respectively. The lag time between peak concentrations of LH and testosterone varied from 35 to 55 min. The calculated maximum response of testosterone to LH, secreted by the anterior pituitary after GnRH injection, was 1.8 times higher than to GnRH. It was concluded that intravenous administration of GnRH induced marked and dose-dependent increases in plasma concentrations of LH and testosterone, and that there does not appear to be a direct effect of GnRH on Leydig cells in male dogs.

Leydig cell number and function in the adult cynomolgus monkey (Macaca fascicularis) is increased by daily hCG treatment but not by daily FSH treatment

Daily treatment of adult cynomolgus monkeys with 450 i.u. hCG for 16 days resulted in a significant 163% increase in the number of Leydig cells, and a 9-fold rise in plasma testosterone concentrations. The number of proliferating Leydig cells was very low, even after 16 days of treatment with hCG. Daily FSH administration (2 injections of 15 i.u. per day) did not have any effect on the number of Leydig cells or plasma testosterone values. It can be concluded, therefore, that in adult cynomolgus monkeys daily hCG treatment results in an increase in the number of Leydig cells, which is mainly caused by the differentiation of precursor cells. Since plasma testosterone concentrations were increased to an even higher extent, the steroid production per Leydig cell was also stimulated.

Sex, plasma lipoproteins, and atherosclerosis: Prevailing assumptions and outstanding questions

We review the hypothesis that the incidence of coronary heart disease (CHD) is higher in men than in women due to differences in plasma lipoprotein risk factors between the sexes. Men and women appear to be equally susceptible to the effects of lipoprotein risk factors for CHD, and the difference between the sexes in lipoprotein risk factors for CHD appears to be consistent with their being, at least in part, responsible for the sex difference in CHD. This is apparent both when men and women of equal age are compared, and when age-related variations in the sex differences in plasma lipoproteins and CHD are considered. Differences between the sexes in lipoprotein concentrations are still present when sex differences in adiposity, cigarette smoking, physical activity, and diet are taken into account. Evidence relating these sex differences in CHD and lipoproteins to the effects of sex hormones is critically examined. It is commonly accepted that androgens induce changes in lipoprotein concentrations that would predispose towards CHD, whereas estrogens are held to have opposite effects. However, much of the evidence for this comes from studies of changes associated with administration of synthetic gonadal steroids or with changes in gonadal function. Studies of differences in lipoprotein metabolism in normal men and women are extremely limited. In males high-density lipoprotein (HDL) cholesterol levels fall at puberty, correlating with the rise in plasma testosterone concentrations. In females, HDL levels do not change at puberty, despite the rise in estrogen concentrations. Evidence for lipoprotein changes during the menopause, when estrogen levels decline, is equivocal. Similarly, the evidence for an increase in CHD incidence at the menopause is inconclusive. National mortality data indicate that the decreasing sex difference in CHD after 50 years of age is due to a declining rate of increase in men rather than to an acceleration in CHD incidence in women. In men the age-related increase in low-density lipoprotein (LDL) concentrations diminishes beyond 50 years of age, whereas in women the rate of increase remains unchanged. Studies of the effects of gonadectomy are of doubtful relevance in assessing the roles of sex hormones in CHD, and have not been performed with sufficient rigor to provide definitive conclusions. The effects of exogenously administered androgens and estrogens on lipoprotein concentrations have dominated the evaluation of the hypothesis that differences in sex hormones underlie the sex difference in lipoprotein concentrations and hence CHD incidence. However, these studies have been confounded by the variety and nature of gonadal steroids employed, with native (nonsynthetic) hormones being poorly represented. The lack of thorough prospective studies of risk factors for CHD in women, comparative studies of lipoprotein metabolism in healthy men and women, and prospective studies relating endogenous sex hormone levels, plasma lipoprotein concentrations, and development of CHD all remain serious omissions in our understanding of the pathogenesis of the major cause of death in Western society.

Testicular volume during early infancy

FOREST/ in 1973, demonstrated a significant rise in the plasma testosterone concentrations of boys during early infancy. Testosterone values increase from birth to 3 months of age, reach a concentration of approximately 300 ng/dl, and then decrease to about 10 ng/dl by 7 months of age. The testosterone surge is associated with a transient elevation of both follicle-stimulating hormone and luteinizing hormone. ~. 3 Values for androstenedione, a steroid primarily of adrenal origin, do not rise during early infancy/. 5 Hence, it has been postulated that this transient rise in plasma testosterone concentration represents an increase in testicular steroidogenic activity, presumably under gonadotropin regulation. ~ Since testicular enlargement is the earliest sign of the pubertal gonadotropin rise in males, we have investigated whether a similar maturational event occurs during early infancy. Accordingly, we have measured the testicular volume of normal boys during the first six months of life.

THE EFFECT OF ACTH ON PLASMA TESTOSTERONE AND ANDROSTENEDIONE CONCENTRATIONS IN PATIENTS WITH PROSTATIC CARCINOMA

The effect of Synacthen (beta1-24-corticotrophin) on plasma testosterone and 4-androstene-3, 17-dione concentrations in untreated patients with prostatic carcinoma, and in patients receiving endocrine therapy is described. An established specific radioimmunoassay was used for the measurement of testosterone, and a radioimmunoassay for 3-androstene-3,17-dione using thin layer chromatography has been developed. Administration of Synacthen resulted in a fall in testosterone in untreated patients, but a rise in 4-androstene-3,17-dione was observed. The plasma concentration of testosterone in all treated patients increased after administration of Synacthen. An increased concentration of plasma 4-androstene-3,17-dione was also observed in these treated patients after Synacthen, but the magnitude of the response was not significantly different from that of untreated patients. The work provides further evidence that in the patient being treated with oestrogen for carcinoma of the prostate a rise in plasma testosterone concentration will result from an increased secretion of ACTH.