Aging alters feed-forward and feedback linkages between LH and testosterone in healthy men

1997 ◽  
Vol 273 (4) ◽  
pp. R1407-R1413 ◽  
Author(s):  
Thomas Mulligan ◽  
Ali Iranmanesh ◽  
Michael L. Johnson ◽  
Martin Straume ◽  
Johannes D. Veldhuis
Keyword(s):  
Feedback Inhibition ◽  
Serum Testosterone ◽  
Older Men ◽  
Older Individuals ◽  
Deconvolution Analysis ◽  
Feed Forward ◽  
Testosterone Secretion ◽  
Serum Lh ◽  
Lh Secretion ◽  
Secretion Rates

To discern the effect of aging on coordinate luteinizing hormone (LH) and testosterone secretion, we sampled healthy older men (age 62–74 yr, n = 11) and young controls (age 21–34 yr, n = 13) every 2.5 min overnight. Deconvolution analysis and cross-correlation were used to relate serum LH concentrations to calculated testosterone secretion rates (feed-forward stimulation), as well as serum testosterone concentrations to computed LH secretion rates (feedback inhibition). Despite statistically similar mean serum LH and testosterone concentrations in the young and older men, older individuals had diminished feed-forward stimulation of LH concentrations on calculated testosterone secretion rates, as well as delayed feedback inhibition of testosterone concentrations on computed LH secretion rates.

Non-responsiveness of serum gonadotropins and testosterone to pulsatile GnRH in hemochromatosis suggesting a pituitary defect

1993 ◽  
Vol 128 (4) ◽  
pp. 351-354 ◽  
Author(s):  
Lise Duranteau ◽  
Philippe Chanson ◽  
Joelle Blumberg-Tick ◽  
Guy Thomas ◽  
Sylvie Brailly ◽  
...  
Keyword(s):  
Single Pulse ◽  
Serum Testosterone ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Gonadotropin Secretion ◽  
Pulsatile Gnrh ◽  
Serum Lh ◽  
Before And After ◽  
Gnrh Therapy ◽  
Lh Secretion

We investigated the potential pituitary origin of gonadal insufficiency in hemochromatosis. Gonadotropin secretion was studied in seven patients with hemochromatosis and hypogonadism, before and after chronic pulsatile GnRH therapy. Pulsatile LH secretion was studied before (sampling every 10 min for 6 h) and after 15-30 days of chronic pulsatile GnRH therapy (10-12 μg per pulse). Prior to GnRH therapy, all the patients had low serum testosterone, FSH and LH levels. LH secretion was non-pulsatile in four patients, while a single pulse was detected in the remaining three. Chronic pulsatile GnRH administration did not increase serum testosterone levels; similarly, serum LH levels remained low: neither pulse frequency nor pulse amplitude was modified. We conclude that hypogonadism in hemochromatosis is due to pituitary lesions.

Explicating hypergonadotropism in postmenopausal women: a statistical model

2000 ◽  
Vol 278 (5) ◽  
pp. R1247-R1257 ◽  
Author(s):  
Daniel M. Keenan ◽  
Johannes D. Veldhuis
Keyword(s):  
Maximum Likelihood ◽  
Luteinizing Hormone ◽  
Slow Component ◽  
Hormone Secretion ◽  
Maximum Likelihood Estimates ◽  
Elimination Kinetics ◽  
Serum Lh ◽  
Constitutive Components ◽  
Lh Secretion ◽  
Secretion Rates

Neurohormone secretion is viewed here as a variable (unknown) admixture of basal and pulsatile release mechanisms, convolved with individually fitted biexponential elimination kinetics. This construct allows maximum-likelihood estimates of both (regulated and constitutive) components of hormone secretion. Thereby, we infer that a prolonged slow-component half-life of gonadotropin removal and amplified pulsatile (and total) daily luteinizing hormone (LH) secretion rates jointly explicate the postmenopausal elevation in serum LH concentrations without a necessary rise in basal LH secretion rates. This biomathematical formulation should be useful in exploring other neuroregulatory mechanisms that underlie single or dual alterations in the basal versus pulsatile modes of hormone secretion.

The contribution of corticosterone and testosterone to the suppression of serum LH in hyperprolactinaemic adult male rats with pituitary transplants

1987 ◽  
Vol 113 (1) ◽  
pp. 111-116 ◽  
Author(s):  
R. F. A. Weber ◽  
M. P. Ooms ◽  
J. T. M. Vreeburg
Keyword(s):  
Adult Male ◽  
Serum Testosterone ◽  
Serum Levels ◽  
Male Rats ◽  
Male Rat ◽  
Serum Concentrations ◽  
Testosterone Secretion ◽  
Accessory Sex Glands ◽  
Serum Lh ◽  
Stimulation Of

ABSTRACT The effects of hyperprolactinaemia on serum levels of LH were investigated in adult male rats of the R × U strain. Hyperprolactinaemia was induced by three pituitary grafts under the kidney capsule, transplanted on day 0 of each experiment. Special attention was paid to the contribution of prolactin-stimulated testes, adrenals and corticosterone. In experiment 1, hyperprolactinaemia significantly reduced the serum concentrations of LH in intact rats. In spite of a significant increase in the serum levels of corticosterone, serum testosterone was not significantly affected by hyperprolactinaemia. The weights of both the adrenals and accessory sex glands were significantly increased at autopsy. In experiment 2, treatment with 10 mg corticosterone s.c. daily from day 14 to day 28 after pituitary grafting significantly reduced serum levels of both LH and testosterone. The suppression of testosterone in the hyperprolactinaemic corticosterone-treated animals was significantly less than in the corticosterone-treated control animals. The weights of the accessory sex glands were significantly increased in the hyperprolactinaemic animals. In experiment 3, rats were adrenalectomized and half of them were substituted with corticosterone. Serum testosterone levels significantly increased in both hyperprolactinaemic adrenalectomized rats and in adrenalectomized corticosterone-treated animals without any significant effect on serum LH. Again the weights of the accessory sex glands were significantly increased in the hyperprolactinaemic animals. In experiment 4, rats were adrenalectomized, gonadectomized and corticosterone treated on day 0 and then implanted with a 2, 1·5 or 1 cm silicone elastomer capsule containing testosterone. On day 28 after pituitary grafting, LH levels were significantly suppressed in animals with a 2 or 1·5 cm testosterone implant. The weights of the accessory sex glands were not increased in the hyperprolactinaemic animals. These results show that in the male rat the inhibitory effects of hyperprolactinaemia on serum LH levels may be due to (1) increased sensitivity of the hypothalamic-pituitary axis to the negative feedback action of testosterone by prolactin and by the prolactin-stimulated corticosterone secretion and (2) stimulation of testicular testosterone secretion by prolactin, which can also explain the increased weights of the accessory sex glands. Even in the presence of high serum concentrations of corticosterone, stimulation of testicular testosterone secretion by prolactin was observed. J. Endocr. (1987) 113,111–116

IMPORTANCE OF THE EPISODIC NATURE OF LUTEINIZING HORMONE SECRETION FOR NORMAL DEVELOPMENT OF THE BOVINE TESTIS DURING PUBERTY: INTERFERENCE WITH OESTRADIOL-17β

1981 ◽  
Vol 88 (3) ◽  
pp. 393-400 ◽  
Author(s):  
B. D. SCHANBACHER
Keyword(s):  
Normal Development ◽  
Pubertal Development ◽  
Hormone Secretion ◽  
Serum Testosterone ◽  
Luteinizing Hormone Secretion ◽  
Testicular Growth ◽  
Serum Lh ◽  
Beef Bulls ◽  
Lh Releasing Hormone ◽  
Lh Secretion

An experiment was conducted to determine the importance of episodic LH secretion during pubertal development in beef bulls. Testicular growth, LH secretory patterns and serum testosterone concentrations were monitored in control bulls, and bulls implanted with one or two oestradiol-filled capsules from 26 to 38 weeks of age. Control but not oestradiol-treated bulls showed normal testicular growth and episodic LH secretory patterns. Serum LH and testosterone responses of 38-week-old control and oestradiol-treated bulls to an intravenous challenge of 5 μg LH releasing hormone indicated normal pituitary responsiveness, but steroidogenic responsiveness had not yet developed in oestradiol-treated bulls. Removal of the capsules at 38 weeks of age resulted in a normal episodic release pattern for LH, with concomitant growth of the underdeveloped testes up to 44 weeks of age. Serum concentrations of LH and testosterone were within the range of normal, adult values by 42 weeks of age. These results suggest that oestradiol can interfere with episodic LH secretion and normal pubertal development in beef bulls, and furthermore that episodic LH secretion is commensurate with the establishment of normal development of the bovine testis during puberty.

scholarly journals Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism

2008 ◽  
Vol 158 (5) ◽  
pp. 741-747 ◽  
Author(s):  
Sandra Loves ◽  
Janneke Ruinemans-Koerts ◽  
Hans de Boer
Keyword(s):  
Hypogonadotropic Hypogonadism ◽  
Serum Testosterone ◽  
Free Testosterone ◽  
Total Testosterone ◽  
Male Hypogonadism ◽  
Serum Lh ◽  
Long Term Effect ◽  
Starting Dose ◽  
Severely Obese ◽  
Lh Secretion

ObjectiveIsolated hypogonadotropic hypogonadism (IHH) is frequently observed in severely obese men, probably as a result of increased estradiol (E2) production and E2-mediated negative feedback on pituitary LH secretion. Aromatase inhibitors can reverse this process. This study evaluates whether letrozole once a week can normalize serum testosterone in severely obese men and maintain its long term effect.DesignOpen, uncontrolled 6-month pilot study in 12 severely obese men (body mass index>35.0 kg/m2) with obesity-related IHH and free testosterone levels <225 pmol/l, treated with 2.5 mg letrozole once a week for 6 months.ResultsSix weeks of treatment reduced total E2 from 123±11 to 58±7 pmol/l (P<0.001, mean±s.e.m.), and increased serum LH from 4.4±0.6 to 11.1±1.5 U/l (P<0.001). Total testosterone rose from 5.9±0.5 to 19.6±1.4 nmol/l (P<0.001), and free testosterone from 163±13 to 604±50 pmol/l (P<0.001). Total testosterone rose to within the normal range in all subjects, whereas free testosterone rose to supraphysiological levels in 7 out of 12 men. The testosterone and E2 levels were stable throughout the week and during the 6-month treatment period.ConclusionLetrozole 2.5 mg once a week produced a sustained normalization of serum total testosterone in obese men with IHH. However, free testosterone frequently rose to supraphysiological levels. Therefore, a starting dose <2.5 mg once a week is recommended.

Influence of anti-oestrogens on gonadotrophin secretion in control and ACTH-infused immature rats

1984 ◽  
Vol 105 (3) ◽  
pp. 308-313 ◽  
Author(s):  
David R. Mann ◽  
Michael S. Blank ◽  
R. Sridaran ◽  
V. Daniel Castracane ◽  
Charles Eldridge ◽  
...  
Keyword(s):  
Serum Testosterone ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Constant Infusion ◽  
Simultaneous Treatment ◽  
Serum Lh ◽  
Gonadotrophin Secretion ◽  
Immature Rats ◽  
Lh Secretion

Abstract. The objective of this study was to determine whether anti-oestrogens (nafoxidine, MER-25) would block the suppressive effects of ACTH on gonadotrophin secretion in immature rats. Female rats were castrated at 25–26 days of age, and an Alzet osmotic minipump containing ACTH (1–24) or saline was implanted in each animal. ACTH was administered at a rate of 1 IU/day by constant infusion. Beginning on the day of surgery, animals were injected daily for 5 days with 0.25, 5 or 25 μg/100 g body weight of nafoxidine or 5 mg MER-25 and sacrificed on the sixth day following castration. ACTH lowered serum LH concentrations and increased pituitary LH levels. Serum androstenedione concentrations were more than two times greater in ACTH-infused than in control rats, but serum oestrone levels were not affected. Serum testosterone and oestradiol concentrations in ACTH-infused rats remained below levels of detection. Administration of 0.25 μg of nafoxidine prevented the suppressive effects of ACTH on serum LH. Serum levels of LH in these animals were comparable to saline-treated controls (418 ± 94 vs 443 ± 73 ng/ml). The two higher doses of nafoxidine and MER-25 were ineffective in suppressing the actions of ACTH on serum LH. MER-25 reduced serum LH values in both controls and ACTH-infused rats. Serum FSH concentrations were not altered by ACTH or nafoxidine treatment. MER-25 elevated pituitary FSH concentrations in both control and ACTH-infused rats. These data suggest that the inhibitory effect of ACTH on LH secretion in immature rats is mediated by an oestrogenic steroid, since this action can be blocked by simultaneous treatment with a low dose of the anti-oestrogen, nafoxidine.

scholarly journals Joint Basal and Pulsatile Hypersecretory Mechanisms Drive the Monotropic Follicle-Stimulating Hormone (FSH) Elevation in Healthy Older Men: Concurrent Preservation of the Orderliness of the FSH Release Process: A General Clinical Research Center Study*

1999 ◽  
Vol 84 (10) ◽  
pp. 3506-3514
Author(s):  
J. D. Veldhuis ◽  
A. Iranmanesh ◽  
L. M. Demers ◽  
T. Mulligan
Keyword(s):  
High Sensitivity ◽  
Approximate Entropy ◽  
Fold Increase ◽  
Older Men ◽  
Older Individuals ◽  
Release Process ◽  
Deconvolution Analysis ◽  
Clinical Research Center ◽  
Lower Amplitude ◽  
Neuroendocrine Mechanisms

Abstract To appraise the neuroendocrine mechanisms that underlie a selective (monotropic) elevation of serum FSH concentrations in healthy older men, we sampled blood in 11 young (ages 21–34) and 8 older men (ages 62–72) men every 2.5 min overnight. Serum FSH concentrations were quantitated in an automated, high-sensitivity, chemiluminescence-based assay. Rates of basal and pulsatile FSH secretion were estimated by deconvolution analysis, and the orderliness of the FSH release process via quantitated the approximate entropy statistic. Statistical analysis revealed that healthy older men manifest dual neuroendocrine hypersecretory mechanisims; specifically, a 2-fold increase in the basel (nonpulsatile) FSH secretion rate, and a concurrent 50% amplification of FSH secretory burst mass (and amplitude). The regularity or orderliness of ad seriatim FSH release is preserved in older individuals. We postulate that higher basel FSH secretion in older men is a consequence of reduced testosterone negative feedback, whereas amplified FSH secretory burst mass reflects net enhanced stimulation of gonadotrope cells by endogenous FSH secretagogues (e.g. GnRH and/or activin). The foregoing specific mechanisms driving heightened FSH secretion in older men contrast with the lower-amplitude pulsatility and more disorderly patterns of LH release in the same individuals. Thus, the present data illuminate an age-dependent disparity in the disruption of FSH neuroregulation in the aging male.

Colony-Stimulating Factor-1 Plays a Major Role in the Development of Reproductive Function in Male Mice

1997 ◽  
Vol 11 (11) ◽  
pp. 1636-1650 ◽  
Author(s):  
Paula E. Cohen ◽  
Matthew P. Hardy ◽  
Jeffrey W. Pollard
Keyword(s):  
Reproductive Tract ◽  
Reproductive Function ◽  
Serum Testosterone ◽  
Hydroxysteroid Dehydrogenase ◽  
Colony Stimulating Factor ◽  
Membrane Structures ◽  
Chain Cleavage ◽  
Serum Lh ◽  
Lh Secretion ◽  
Stimulating Factor

Abstract Colony-stimulating factor-1 (CSF-1) is the principal regulator of cells of the mononuclear phagocytic lineage that includes monocytes, tissue macrophages, microglia, and osteoclasts. Macrophages are found throughout the reproductive tract of both males and females and have been proposed to act as regulators of fertility at several levels. Mice homozygous for the osteopetrosis mutation (csfmop) lack CSF-1 and, consequently, have depleted macrophage numbers. Further analysis has revealed that male csfmop/csfmop mice have reduced mating ability, low sperm numbers, and 90% lower serum testosterone levels. The present studies show that this low serum testosterone is due to reduced testicular Leydig cell steroidogenesis associated with severe ultrastructural abnormalities characterized by disrupted intracellular membrane structures. In addition, the Leydig cells from csfmop/csfmop males have diminished amounts of the steroidogenic enzyme proteins P450 side chain cleavage, 3β-hydroxysteroid dehydrogenase, and P450 17α-hydroxylase-lyase, with associated reductions in the activity of all these steroidogenic enzymes, as well as in 17β-hydroxysteroid dehydrogenase. The CSF-1-deficient males also have reduced serum LH and disruption of the normal testosterone negative feedback response of the hypothalamus, as demonstrated by the failure to increase LH secretion in castrated males and their lack of response to exogenous testosterone. However, these males are responsive to GnRH and LH treatment. These studies have identified a novel role for CSF-1 in the development and/or regulation of the male hypothalamic-pituitary-gonadal axis.

scholarly journals Age and time-of-day differences in the hypothalamo–pituitary–testicular, and adrenal, response to total overnight sleep deprivation

SLEEP ◽  
2020 ◽  
Vol 43 (7) ◽  
Author(s):  
Peter Y Liu ◽  
Paul Y Takahashi ◽  
Rebecca J Yang ◽  
Ali Iranmanesh ◽  
Johannes D Veldhuis
Keyword(s):  
Sleep Deprivation ◽  
Older Men ◽  
Pulse Frequency ◽  
Time Of Day ◽  
Regulatory Control ◽  
Sleep Restriction ◽  
Older Individuals ◽  
Deconvolution Analysis ◽  
Age Related ◽  
Adrenal Response

Abstract Study Objectives In young men, sleep restriction decreases testosterone (Te) and increases afternoon cortisol (F), leading to anabolic–catabolic imbalance, insulin resistance, and other andrological health consequences. Age-related differences in the hypothalamo–pituitary–testicular/adrenal response to sleep restriction could expose older individuals to greater or lesser risk. We aimed to evaluate and compare the 24-h and time-of-day effect of sleep restriction on F, luteinizing hormone (LH), and Te in young and older men. Methods Thirty-five healthy men, aged 18–30 (n = 17) and 60–80 (n =18) years, underwent overnight sleep deprivation (complete nighttime wakefulness) or nighttime sleep (10 pm to 6 am) with concurrent 10-min blood sampling in a prospectively randomized crossover study. F, LH, and Te secretion were calculated by deconvolution analysis. Results Sleep deprivation had multiple effects on 24-h Te secretion with significant reductions in mean concentrations, basal, total and pulsatile secretion, and pulse frequency (each p &lt; 0.05), in the absence of detectable changes in LH. These effects were most apparent in older men and differed according to age for some parameters: pulsatile Te secretion (p = 0.03) and Te pulse frequency (p = 0.02). Time-of-day analyses revealed that sleep restriction significantly reduced Te in the morning and afternoon, reduced LH in the morning in both age groups, and increased F in the afternoon in older men. Conclusions These data suggest a time-of-day dependent uncoupling of the regulatory control of the testicular axis and of F secretion. Future studies will need to directly verify these regulatory possibilities specifically and separately in young and older men. Clinical Trial Not applicable.

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