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Background: Male testosterone levels decline by 1% per year from the age of 40 years. Whilst a primary testicular deficit occurs, hypothalamic or pituitary dysregulation may also coexist. This study aimed to compare the hypothalamic response to kisspeptin-54 and the pituitary response to gonadotropin-releasing hormone (GnRH) of older men with those of young men., Methods: Following 1 h of baseline sampling, healthy older men (n = 5, mean age 59.3 ± 2.9 years) received a 3-h intravenous infusion of either vehicle, kisspeptin-54 0.1, 0.3, or 1.0 nmol/kg/h or GnRH 0.1 nmol/kg/h, on five different study days. Serum gonadotropins and total testosterone were measured every 10 min and compared to those of young men (n = 5/group) (mean age 28.9 ± 2.0 years) with a similar body mass index (24 kg/m2) who underwent the same protocol., Results: Kisspeptin-54 and GnRH significantly stimulated serum gonadotropin release in older men compared to vehicle (p < 0.001 for all groups). Gonadotropin response to kisspeptin-54 was at least preserved in older men when compared to young men. At the highest dose of kisspeptin-54 (1.0 nmol/kg/h), a significantly greater luteinising hormone (LH) (p = 0.003) response was observed in older men. The follicle-stimulating hormone (FSH) response to GnRH was increased in older men (p = 0.002), but the LH response was similar (p = 0.38). Serum testosterone rises following all doses of kisspeptin-54 (p ≤ 0.009) were reduced in older men., Conclusions: Our data suggest that healthy older men without late-onset hypo-gonadism (LOH) have preserved hypothalamic response to kisspeptin-54 and pituitary response to GnRH, but impaired testicular response. Further work is required to investigate the use of kisspeptin-54 to identify hypothalamic deficits in men with LOH., (The Author(s). Published by S. Karger AG, Basel.)

The development of the catfish gonadotropin-releasing hormone (cfGnRH) fiber network in the pituitary of male African catfish (Clarias gariepinus) was investigated in relation to puberty. Double immunolabeling studied by confocal laser scanning microscopy revealed a concomitant development of gonadotropes and of pituitary cfGnRH innervation during the first wave of spermatogenesis. Catfish GnRH-immunoreactive fibers in the proximal pars distalis (PPD) of the pituitary were initially observed at the age of 10 weeks (onset of spermatogonial proliferation) and gradually reached the adult pattern at the age of 20 weeks (spermatozoa present in the testis). The content of cfGnRH-associated peptide (cfGAP, part of the prohormone) in the pituitary similarly increased during puberty. At the electron microscopical level, fibers containing cfGAP-ir granules came into close proximity of the gonadotropes at 18 weeks of age. In vitro studies indicated a progressively increasing basal and cfGnRH-stimulated luteinizing hormone (LH) secretion during pubertal development. The LH secretion patterns were similar in response to exogenous cfGnRH (0.1 microM) or to endogenous cfGnRH, the release of which was induced by forskolin (1 microM). Castration experiments demonstrated that the innervation of the pituitary with cfGnRH fibers continued after surgery, accompanied by an increase in the cfGAP levels. However, gonadotrope development was retarded, suggesting a differential regulation of the two maturational processes. Since testosterone stimulates both processes, other testicular factors may also be involved. Puberty-associated changes in LH release patterns appear to reflect changes in the GnRH sensitivity and in the pool of releasable LH, while availability of cfGnRH does not appear to be a limiting factor., (Copyright 2000 S. Karger AG, Basel)

The aim of the present experiments was to determine whether some rationale for the presence of the several inhibitory neurotransmitters in the innervation to the toad melanotroph might be found in differences in their individual effects or in possible cooperative interactions affecting secretion. Measurements of peptide release from isolated, perifused neurointermediate lobes of the toad Xenopus laevis showed that each of the three identified inhibitory transmitters, dopamine, GABA and NPY, was able to inhibit secretion profoundly and no less effectively than omission of Ca. Moreover, the inhibitory effects were rather similar in onset, duration and recovery. Furthermore, there was no evidence of any cooperative interactions when the transmitters were given in various combinations. And finally, the inhibitory response to each of the transmitters was abolished by pretreatment with pertussis toxin. While not excluding differential postsynaptic effects on other parameters of melanotroph function, the similarities observed have encouraged alternative speculations on the significance of the apparent redundancy of inhibitory transmitters.

In this study we have investigated the presence of nerve fibers containing dopamine, thyrotropin-releasing hormone (TRH) and neuropeptide Y (NPY) in the pars intermedia of the crested newt and we have examined the possible effect of these neurohormones on the release of alpha-melanotropin (alpha-MSH) by neurointermediate lobes in vitro. By means of immunohistochemistry, we observed the presence of tyrosine hydroxylase (TH)-immunoreactive fibers in the pars intermedia of the crested newt. Using a specific antiserum to dopamine, these fibers appeared to be mainly dopaminergic in nature. Unlike anurans, urodele amphibians do not exhibit TRH or NPY-like immunoreactivity in the pars intermedia. A perifusion system technique for newt pituitaries was developed to investigate the effect of dopamine, TRH and NPY on alpha-MSH secretion. Administration of increasing concentrations of dopamine (from 10(-9) to 10(-5)M) induced a dose-related inhibition of alpha-MSH release. This inhibitory effect was mimicked by the dopamine agonist apomorphine (10(-6)M). In contrast, the secretory activity of the newt pars intermedia was not affected by administration of synthetic TRH or NPY (up to 10(-7) and 10(-6)M, respectively). These results indicate that the neurotransmitter dopamine likely plays a pivotal role in the regulation of melanotropin secretion in urodele amphibians.

Catecholamines were measured in the separated intermediate and posterior lobes of the rat after stalk section and bilateral superior cervical ganglionectomy. In the intermediate lobe, after stalk section, dopamine decreases 96%, norepinephrine decreases 80%, and epinephrine is undetectable. In the posterior lobe, dopamine and epinephrine are absent, and norepinephrine decreases by 70% after the operation. In contrast, bilateral superior cervical ganglionectomy produces only a 40% decrease in norepinephrine in the posterior lobe, and no changes in catecholamines in the intermediate lobe. Our results demonstrate that most of the intermediate and posterior pituitary catecholamines are present in nerve fibers of brain origin, and that the posterior lobe has a dual norepinephrine innervation, partly originating in the superior cervical ganglia.

To determine the sites of action whereby estradiol (E2) induces the preovulatory luteinizing hormone (LH) surge in pigs, hypophysial-stalk-transected (HST) ovariectomized (OVX) gilts (mean +/- SE: 118 +/- 12 kg) received intramuscular injections of E2 benzoate (10 micrograms E2B/kg body weight) on day 0, plus intravenous pulses of 1 microgram gonadotropin-releasing hormone (GnRH) every 45 min either from days -5 to 4, days -5 to 0 or days -5 to 0 then days 2 to 4. A fourth and fifth group received steroid vehicle on day 0 and pulses of GnRH on either days -5 to 4 or days -5 to 0 then days 2 to 4. In stalk-intact OVX gilts, E2B inhibited LH release for 48 h, then induced an LH surge that peaked 60-84 h after steroid treatment. In HST OVX gilts, serum LH increased from undetectable concentrations (less than 0.17 ng/ml) to 0.42 +/- 0.03 ng/ml after 5 days of pulsatile GnRH replacement. In the presence of pulsatile GnRH stimulation, serum LH concentrations were inhibited for 12 h after E2B but then returned to values that were similar to those for HST gilts given GnRH in the absence of steroid treatment. Discontinuing GnRH pulses at the time of E2B injection caused serum LH concentrations to drop to 0.18 ng/ml or less for the remaining 96 h. When GnRH pulses were interrupted for 48 h, beginning immediately after injecting E2B or vehicle to mimic the secretory hiatus of LH and presumably GnRH observed in stalk-intact pigs prior to the surge, resumption of GnRH pulses caused serum LH concentrations to increase progressively over 3 h in E2B-treated gilts but to peak abruptly in controls given vehicle.(ABSTRACT TRUNCATED AT 250 WORDS)