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Ontogeny of pulsatile luteinizing hormone and testosterone secretion in male lambs.

The ontogeny of pulsatile LH and testosterone (T) secretion was studied in the developing male sheep. Three variables of LH secretion (frequency of LH pulses, magnitude of LH pulses, and the levels between pulses) were determined during a 6-h period at each of 1, 2, 3, 5, 7, 8, 12, and 16 weeks of age in six male lambs. Pulsatile LH secretion was evident by 1-2 weeks of age in rapidly growing lambs and by 3-7 weeks of age in slowly growing lambs. Although mean height of LH discharges increased 2-fold after the onset of pulsatile release, levels between discharges remained constant throughout the entire study. The most striking change, however, occurred in the frequency of LH discharges. The frequency increased 20-fold between weeks 1 and 8 and then decreased 3-fold between weeks 8 and 16. In each lamb, a brief (less than 3 h), but marked rise (greater than 2 ng/ml) in levels of circulating T occurred after the first observed pulse of LH. Thereafter, as the lambs became older, increased concentrations of serum T were observed only during periods of pulsatile LH secretion, the highest mean level of T occurring about 1 h after each LH peak. Administration of human chorionic gonadotropin (hCG) iv to 2-day-old males resulted in a marked increase in circulating T. A greater increment in concentrations of serum T occurred after the same absolute dose (50 IU) of hCG at 8 weeks of age than at 2 days of age. These results indicate that in the male lamb 1) pulsatile secretion of LH is initiated shortly after birth and changes in mean levels of LH are primarily a reflection of changes in frequency of LH discharges; 2) before the onset of pulsatile LH secretion, the testes are capable of responding to an exogenous LH-like gonadotropin with increased secretion of T; 3) after the onset of pulsatile LH secretion, a rise in circulating T follows each pulse of LH; and 4) an increase in capacity of the testes to secret T occurs during the first 8 weeks of postnatal life. It is concluded that the pattern of LH secretion, coupled with the capacity of the testes to secrete T, determines the pattern and magnitude of T secretion in the developing male sheep.

Animals↗

Effect of polychlorinated biphenyls on spermatogenesis and testosterone secretion in adult cocks.

The effects of polychlorinated biphenyls (PCBs) on reproduction of adult cocks were studied by gavaging peanut oil or PCBs (Aroclor 1254, 50 mg/kg) once a week for six consecutive weeks. Physiological parameters were recorded and gonads were removed at the end of experiment for histological examination. The results showed that there was no significant difference between the control and treatment group in body weight, respiration rate, heart rate, body temperature, and the numbers of red and white blood cells. However, there was a marked decrease in the testicular weight and serum testosterone level after PCB treatment. Morphological studies manifested severe damage of the seminiferous tubules by PCB. The number of the germ cells at the different developmental stages was decreased and condensed nuclei were observed in most of these cells. This study revealed that the reproductive function of the adult cocks is sensitive to PCBs, which inhibited mainly spermatogenesis and testosterone secretion.

Administration, Oral↗

Empty sellae, impaired testosterone secretion, and defective hypothalamic-pituitary growth and gonadal axes in children with Bardet-Biedl syndrome.

We evaluated growth parameters and hypothalamic-pituitary-gonadal and growth functions in five children with Bardet-Biedl syndrome (BBS). Three of the five children had stature below the fifth percentile for age. Their growth hormone (GH) response to provocation was defective, and computed tomographic (CT) scanning revealed empty sellae in all of them. All the children were obese (body mass index [BMI] > 95th percentile for age). Three had hypercholesterolemia. Their basal serum testosterone concentration and testosterone response to 3-day human chorionic gonadotropin (HCG) stimulation were significantly lower than the levels in 12 age-matched obese normal children. Testosterone secretion failed to respond to HCG therapy for 4 weeks. Both basal gonadotropin levels (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and gonadotropin responses to LH-releasing hormone (LHRH) stimulation were normal and did not differ among the two study groups. It appears that primary hypogonadism is a cardinal feature of BBS, and it may be accompanied by hypothalamic and pituitary abnormalities.

Adolescent↗

Enhancement of testosterone secretion by normal adult human Leydig cells by co-culture with enriched preparations of normal adult human Sertoli cells.

An in-vitro method was developed to study Sertoli-Leydig cell interactions in man, using testes removed at the time kidneys were removed for transplantation from 6 young adult men (aged 17-45 years) after cerebral death. After collagenase digestion of testicular tissue, Leydig cells were purified on discontinuous Percoll gradients. Two fractions of Leydig cells, 'L2' and 'L3' which differed in their buoyant density (1.05 g < L2 < 1.06 g and 1.06 g < L3 < 1.08 g), were obtained. The Sertoli cell-enriched preparation was obtained from seminiferous tubular fragments after sequential treatment with glycine buffer to remove peritubular-myoid cells, a second collagenase digestion, mechanical fragmentation and washes to remove germ cells. Purified Leydig cells were then cultured either alone or together with Sertoli cells in culture dishes coated with collagen, fibronectin and laminin in a chemically defined medium without serum. The influence of co-culture on basal testosterone secretion was examined in 3 successive 48 h periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Amplified nocturnal luteinizing hormone (LH) secretory burst frequency with selective attenuation of pulsatile (but not basal) testosterone secretion in healthy aged men: possible Leydig cell desensitization to endogenous LH signaling--a clinical research center study.

The specific mechanisms underlying the relative hypogonadism of aging remain to be elucidated fully. We used frequent venous sampling (every 2.5 min), sensitive and specific LH and testosterone assays, and deconvolution analysis of the endocrine time series to delineate the differences between healthy young (n = 10, age 21-34 yr) and aged (n = 8, age 62-74 yr) men in the nocturnal secretion of LH and testosterone and their half-lives. We found that elderly men vs. young men had more frequent bursts of LH secretion (1.4 vs. 0.9/h, P = 0.003), less testosterone secreted per testosterone secretory burst (9.2 vs. 17.0 nmol/L, P = 0.021), and less testosterone secreted per hour (10.7 vs. 25.0 nmol/L.h, P = 0.05). As the frequency of nocturnal LH secretory bursts increased, the frequency of testosterone bursts decreased (r = -0.746, P = 0.034). We conclude that healthy aging is associated with diminished nocturnal testosterone production attributable to 1) a decrement in the mass of testosterone released per burst and 2) an inadequate response by the pituitary gland to enhance testosterone production via an accelerated LH secretory pulse frequency. We speculate that this may reflect a partial desensitization of Leydig cells to LH.

Adult↗

[Depression of testosterone secretion in male patients with respiratory failure].

To investigate the changes of testosterone (T) secretion under sustained hypoxia, we determined basal levels of urine T, 17 ketosteroid, luteinizing hormone releasing hormone (LHRH), luteinizing hormone (LH), follicle stimulating hormone (FSH) and response to LHRH and HCG (human chorionic gonadotropin) in male patients with respiratory failure. After evaluating blood gas data, we also measured serum T, LH, FSH, plasma progesterone (P) and 17 hydroxyprogesterone (17OH-P). The subjects were divided into 3 groups according to PaO2; Group 1 with a PaO2 under 60 Torr, Group 2 with a PaO2 between 60 Torr and under 70 Torr, Group 3 was an age-matched control group. Urine T and serum T were significantly lower in Group 1 compared with those of Group 3. In the LHRH test, augmented relative responsiveness and delayed peak value in LH secretion were observed in Group 1, compared with those of Group 3. As for the HCG test, no differences were observed among the 3 groups. The ratio of 17OH-P to P, which indicates activity of 17-hydroxylase, was observed to be diminished with increasing degrees of hypoxia. These data suggest that in male patients with respiratory failure there was depression in T secretion as well as 17-hydroxylase activity due to hypothalamic-pituitary hypofunction.

Adult↗

Effect of corticosteroids on estradiol and testosterone secretion by granulosa cells in culture.

Effect of corticosteroids on testosterone and estradiol secretion of FSH-primed pig granulosa cells were studied. Cortisol, corticosterone, deoxycorticosterone, deoxycorticosterone acetate and aldosterone enhanced testosterone synthesis, whereas cortisone and dexamethasone were found without effect. Maximal production of testosterone by granulosa cells cultured in delta-4-androstenedione supplemented medium was not further enhanced by addition of DOC. On the contrary, an inhibitory effect of corticosteroids on estradiol secretion in the presence of delta 4-androstenedione was observed. The inhibitory effect of corticosteroids on aromatisation was compared with that of the known aromatase inhibitor 4-androsten-17 beta-ol-3-one acetate. The addition of 4-androsten-17 beta-ol-3-one acetate and DOC to the culture medium supplemented with delta 4-androstenedione resulted in a marked decrease of estradiol synthesis. DOC decreased dbcAMP stimulated estradiol secretion. The results support the idea that corticosteroids may act as modulators of granulosa cell steroidogenesis and thus determine, at least partially, further follicular development or atresia.

Adrenal Cortex Hormones↗

Dose and time relationships of intravenously injected rat recombinant luteinizing hormone and testicular testosterone secretion in the male Rat.

The ability of hCG and LH to induce testosterone (T) secretion by Leydig cells is well documented. However, the influence of the pulsatile nature of LH secretion, with varying frequency and amplitude, on T production in vivo is less clear. In our earlier studies on the relationship between pulsatile LH release and T secretion in adult male rats, no simple causality was observed. The recent availability of rat recombinant (rec) LH prompted us to study the effects of one and of three i.v. pulses of different doses of rat recLH on T secretion in adult male rats rendered hypogonadotropic by treatment with the GnRH antagonist cetrorelix. One or three supraphysiological pulses of 1.0 microg of rat recLH produced similar maximal T responses. In contrast, high physiological LH pulses (0.1 microg) produced discrete T-response peaks, whereas multiple low pulses of LH (0.03 microg) were needed before a T response was achieved. The T stimulation was greatly diminished after an LH pulse of 0.1 microg if rats had been treated on the previous day with pulses of 0.03 vs. 0.1 microg rat recLH, apparently because of prolonged LH deprivation and lack of Leydig cell priming due to the GnRH antagonist treatment. The novel preparation of rat recLH provides a physiologically relevant tool for studying the complex relationship between pulsatile LH release and T secretion in male rats.

Animals↗

Aging attenuates both the regularity and joint synchrony of LH and testosterone secretion in normal men: analyses via a model of graded GnRH receptor blockade.

Testosterone (T) secretion declines in the aging male, albeit for unknown reasons. From an ensemble perspective, repeated incremental signaling among gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and T is required to maintain physiological androgen availability. Pattern-regularity statistics, such as univariate approximate entropy (ApEn) and bivariate cross-ApEn, provide specific and sensitive model-free measurement of altered multi-pathway control. The present study exploits partial muting of one pathway (GnRH drive) to appraise adaptive regulation of LH and T secretion in young and aging individuals. Analyses comprised 100 paired 18-h LH and T concentration time series obtained in 25 healthy men ages 20-72 yr each administered placebo and three graded doses of a specific GnRH-receptor antagonist. Graded blockade of GnRH drive increased the individual regularity of LH and T secretion and the synchrony of LH-T feedforward and T-LH feedback in the cohort as a whole (P<0.001 for each). However, age markedly attenuated ganirelix-induced enhancement of univariate T orderliness and bivariate LH-T feedback and T-LH feedback synchrony (P <or= 0.0025). In summary, the present analyses support the thesis that aging disrupts coordinate control of T secretion, LH-T feedforward, and T-LH feedback in healthy men. Thus the experimental strategy of stepwise silencing of an agonistic pathway may have utility in dissecting the bases of altered neurohormonal linkages in other systems.

Adult↗

Suppression of luteinizing hormone and testosterone secretion in bulls following adrenocorticotropin hormone treatment.

The present investigation was conducted to evaluate the inhibitory effects of adrenal corticosteroids on testosterone production by the bull testis. Administration of a single i.v. dose of adrenocorticotropic hormone (ACTH; 80 IU) resulted in a corticosteroid peak which lasted approximately 6 h. During this 6 h period, no episodic increases in secretion of LH or testosterone were initiated and basal concentrations of testosterone were suppressed (P less than 0.05) below control values. Episodic secretion of LH and testosterone resumed 6--7 h after ACTH when concentrations of serum corticosteroids had returned to basal levels. These results suggest that ACTH-induced increases in serum corticosteroids suppress the episodic secretion of LH, resulting in a suppression of testosterone secretion by the bull testis.

Adrenal Cortex Hormones↗

Age-specific changes in the regulation of LH-dependent testosterone secretion: assessing responsiveness to varying endogenous gonadotropin output in normal men.

Pulsatile and thus total testosterone (Te) secretion declines in older men, albeit for unknown reasons. Analytical models forecast that aging may reduce the capability of endogenous luteinizing hormone (LH) pulses to stimulate Leydig cell steroidogenesis. This notion has been difficult to test experimentally. The present study used graded doses of a selective gonadotropin releasing hormone (GnRH)-receptor antagonist to yield four distinct strata of pulsatile LH release in each of 18 healthy men ages 23-72 yr. Deconvolution analysis was applied to frequently sampled LH and Te concentration time series to quantitate pulsatile Te secretion over a 16-h interval. Log-linear regression was used to relate pulsatile LH secretion to attendant pulsatile Te secretion (LH-Te drive) across the four stepwise interventions in each subject. Linear regression of the 18 individual estimates of LH-Te feedforward dose-response slopes on age disclosed a strongly negative relationship (r = -0.721, P < 0.001). Accordingly, the present data support the thesis that aging in healthy men attenuates amplitude-dependent LH drive of burst-like Te secretion. The experimental strategy of graded suppression of neuroglandular outflow may have utility in estimating dose-response adaptations in other endocrine systems.

Adult↗

Testosterone secretion in children with undescended testis.

Testicular testosterone (T) production was examined in thirty boys with undescended testes (UT) following the administration of 4500 U gonadotropic hormone. Twenty boys had bilateral UT and ten had UT plus hypospadias. As for possible causes of reduced Leydig cell activity it was investigated whether the testis was (1) hypoplastic; (2) abnormally fused with the epididymis; (3) located in the abdomen; (4) or UT was associated with hypospadias. Average T values were significantly lower when the testicle was hypoplastic or its fusion with the epididymis was imperfect; but remained largely undiminished when the testicle was located in the abdomen or when UT was combined with hypospadias. The occurrence of both pathologic and physiologic T reactions in each of the four groups suggests that the population of UT children is heterogeneous, probably due to differences in aetiology and in intrauterine hormonal processes. In the case of UT and hypoplasia the time and method of operation (orchidopexy) must be selected with utmost care, bearing in mind that an originally small testicle with impaired T secretion may become physiologic by the time of puberty.

Abnormalities, Multiple↗

Lactate and the effects of exercise on testosterone secretion: evidence for the involvement of a cAMP-mediated mechanism.

The effects of swimming and lactate on the release of testosterone were examined in male rats. During in vivo experiments, male rats were catheterized via the right jugular vein and blood was collected at 0, 10, 15, 30, and 60 min following the exercise, or they were catheterized via the right jugular vein and the left femoral vein and blood was collected at 0, 2, 5, 10, 15, 30, 60, and 120 min after a 10-min infusion at lactate (13 mg.kg-1.min-1). Trunk blood and blood from the testicular vein were also collected after 10 min of swimming or water immersion. In an in vitro experiment, testicular fragments were challenged with lactate (0.01-10 mM) and/or human chorionic gonadotropin (hCG; 0.5 IU.mL-1), and the mediobasal hypothalamus (MBH) was challenged with lactate (8 mM). The post-exercise levels of plasma lactate and testosterone at 10, 15, and 30 min were higher than resting levels. Plasma luteinizing hormone (LH) was increased following 30 min of swimming. Administration of lactate or hCG increased in a dose dependent manner testicular cyclic adenosine 3':5' monophosphate (cAMP) and testosterone release. Plasma testosterone increased after swimming and lactate infusion. Incubation of MBH with lactate increased the gonadotropin-releasing hormone (GnRH) level in the medium. These results suggest that the increased plasma testosterone levels in male rats during exercise is at least partially a result of a direct and LH-independent stimulatory effect of lactate on the secretion of testosterone by increasing testicular cAMP production. Swim-elevated plasma LH may be a result of a rise of GnRH caused by lactate.

Animals↗

Right occipital cortex suppresses male rat testosterone secretion by a pituitary-independent mechanism.

OBJECTIVES: In addition to being regulated by the hypothalamo-hypophyseal system, testosterone (T) secretion is influenced by a number of less understood mechanisms. The aim of the present study was to examine whether defined areas of the right cerebral cortex could modulate T production. METHODS: In adult male Wistar rats right frontal or occipital decortication, anterior or posterior callosotomy and corresponding sham-operations were performed. After 7-day survival time, T secretion in vitro, serum T and LH concentrations were measured by RIA. RESULTS: Right occipital decortication and posterior callosotomy resulted in an increase in T secretion in vitro when compared to the corresponding sham-operated controls. In contrast, right frontal decortication or anterior callosotomy did not interfere with steroidogenesis. Serum LH concentration was not altered by any interventions. CONCLUSION: The right occipital but not the right frontal cortex is involved in the control of T secretion. The caudal part of the corpus callosum accommodating the fibers originating from the occipital cortex might have a similar function. The fact that LH remained unchanged in all experimental groups suggests that the right occipital cortex and the caudal part of the corpus callosum influence testicular steroidogenesis by a pituitary-independent mechanism.

Animals↗

Role of testosterone secretion and penile reflexes in sexual behavior and sperm competition in male rats: a theoretical contribution.

A number of experiments have documented that when male rats are exposed to female rats they undergo a marked increase in the secretion of luteinizing hormone and testosterone. This response can be conditioned to other, previously neutral, stimuli associated with mating. Recent work has highlighted the remarkable sensitivity of penile reflexes to fluctuations in blood concentration of testosterone. Other work has pointed to the function of penile reflexes in seminal plug removal and deposition. It is hypothesized that penile reflexes are potentiated by the increase in testosterone that occurs in response to sexually relevant cues and that the potentiated reflexes play a role in sperm competition during multi-male mating encounters. The sperm competition centers around a male rat's ability to dislodge seminal plugs left in the vagina by other males and to deposit his own plug as tightly as possible to resist dislodgement by another.

Animals↗

Effects of evodiamine on the secretion of testosterone in rat testicular interstitial cells.

Evodiamine, a bioactive component isolated from the Chinese medicine Wu-chu-yu, exhibits vasodilative and antianoxic action. Although evodiamine indeed has many biological effects, its effects on the endocrine system are not clear. The present study explored the effects of evodiamine on testosterone secretion in vitro. Rat collagenase-dispersed testicular interstitial cells (TICs) were incubated with evodiamine (0 to 10(-4) mol/L) in the presence or absence of human chorionic gonadotropin (hCG), forskolin, 8-bromo-adenosine 3':5'-cyclic monophosphate (8-Br-cAMP), or steroidogenic precursors (including 25-hydroxycholesterol, pregnenolone, progesterone, 17alpha-hydroxyprogesterone, and androstenedione) at 34 degrees C for 1 hour. The testosterone concentration in the media samples was measured by radioimmunoassay. Evodiamine 10(-4) mol/L was effective to reduce both basal and hCG-stimulated testosterone secretion in rat TICs after 1, 2, or 4 hours of incubation. The stimulatory effect of forskolin on testosterone release in TICs was prevented by administration of evodiamine. Evodiamine 10(-4) mol/L also decreased 8-Br-cAMP- and androstenedione-stimulated testosterone secretion. These results suggest that evodiamine reduces testosterone secretion in rat TICs via a mechanism involving reduced activity of cAMP-related pathways and 17beta-hydroxysteroid dehydrogenase (17beta-HSD).

Animals↗

Testosterone secretion, musth behaviour and social dominance in captive male Asian elephants living near the equator.

Testosterone concentrations were measured in blood samples collected weekly over a 5 year period from six adult (19-40 year old) male Asian elephants (Elephas maximus maximus) living in captivity in Sri Lanka (7 degrees N), to investigate the relationship between androgen secretion and the occurrence of musth (temporal gland secretion, drip urination and aggressive behaviour). The testosterone profiles were very variable both within and between animals. Long-term phasic changes in blood concentrations of testosterone, associated with periods of musth, occurred in three of the six elephants, with the most pronounced cyclicity in the oldest animal. Musth occurred annually after periods of high androgen secretion and there was a positive correlation between the duration of musth and mean concentrations of testosterone during the previous 2 months. The time of musth, while consistent for an individual, was variable between animals. In four bulls living within one social group, there was a positive correlation between social rank and mean concentrations of testosterone over the 5 year study, and only the dominant animal showed periodic musth. Short-term changes in testosterone concentrations occurred in blood samples collected every 15 min for 7 h, and following the injection of 20 micrograms GnRH, consistent with regulation through the pulsatile secretion of LH. Overall, the results support the view that fully mature male Asian elephants living near the equator express an asynchronous, cyclical, circannual pattern of gonadal activity, with the cyclical pattern developing progressively from 20 to 40 years of age. The periodic increase in testosterone secretion during the gonadal cycle induces the development of musth; however, androgen withdrawal following a period of hypersecretion may be the cause of some aspects of musth behaviour (aggression, unpredictability, disobedience) which make bull elephants very difficult to manage in captivity.

Animals↗