Carlos A. Nagle

Bio: Carlos A. Nagle is an academic researcher from Universidad del Salvador. The author has contributed to research in topics: Pinealectomy & Melatonin. The author has an hindex of 21, co-authored 42 publications receiving 990 citations.

Is infancy a quiescent period of testicular development? Histological, morphometric, and functional study of the seminiferous tubules of the cebus monkey from birth to the end of puberty.

Abstract: The objective of this study was to describe the maturational changes observed in the seminiferous tubules of the monkey Cebus apella, a New World primate species, from birth to the end of puberty. Nineteen animals were subdivided into four groups: neonatal (1-40 days), infantile (4 months to 1 yr), early pubertal (1 yr, 8 months to 2 yr, 9 months), and late pubertal (4-8 yr). Volumetric determinations of different testicular components were made, tubule diameter and length were calculated, and spermatogenic cells, Sertoli cells, and androgen-binding protein secretion were quantified. Testicular and seminiferous tubule volumes increased significantly in the first 5 months of life and during puberty due to the combined increment in seminiferous tubule diameter and length. The total number of spermatogonia increased until late puberty to stabilize subsequently. Spermatocytes and spermatids appeared during puberty and increased dramatically until the end of this period. The germ cell ratios, indicative of spermatogenic efficiency, improved continuously in late puberty coincidentally with a reduction of spermatocyte degeneration. Sertoli cells proliferated in the neonatal and infantile periods, determining a longitudinal growth of the seminiferous tubules, but remained stable during puberty, when androgen-binding protein secretion increased significantly. The multiplication of germ cells is the main factor responsible for the increment in tubule diameter during puberty and determines the most noticeable postnatal modification of testicular volume. During late puberty, the reduction of spermatocyte degeneration leads to an increment in germ cell ratios and a progressive, but slow, improvement of spermatogenic efficiency, explaining why pubertal development of the testis occurs over such a prolonged period in this primate. This is in contrast to what happens in most laboratory animals and suggests that the Cebus is a useful model for studies of human male puberty.

Effects of melatonin on neurotransmitter uptake and release by synaptosome-rich homogenates of the rat hypothalamus

Abstract: Preincubation of synaptosome-rich homogenates of rat hypothalamus with melatonin resulted in significant decreases of norepinephrine, serotonin, dopamine and glutamate uptake. Melatonin inhibition was noncompetitive; apparent Km's of initial uptake processes were: (2.5 +/- 0.3) x 10(-7) M for norepinephrine, (2.6 +/- 0.3) x 10(-7) M for serotonin, (2.4 +/- 0.4) x 10(-7) M for dopamine and (1.0 +/- 0.3) x 10(-7) M for glutamate. Apparent Ki's for melatonin inhibition of transmitter uptake were: 0.64 +/- 0.14 mM (norepinephrine), 0.23 +/- mM (serotonin), 0.51 +/- 0.08 mM (dopamine) and 1.21 +/- 0.10 mM (glutamate). Transmitter release evoked by increasing [K+] in medium to 30 mM was augmented by melatonin in a dose-dependent manner. Maximal effects were observed on serotonin release. Accumulation of 3H-melatonin within synaptosome-rich homogenates did not exhibit differences between 0 and 37 degrees C, indicating that the uptake of the hormone was not an active process. These results suggest that exogenously-administered melatonin may affect neurotransmitter accumulation and release in the hypothalamus by modification of the transmitter uptake mechanism rather than by competition with the transmitter for its uptake pump.

Effects of Estradiol on Melatonin and Protein Synthesis in the Rat Pineal Organ

Abstract: The effects of estradiol on pineal function haveinsofar been studied by administering supramaximal, non-physiological doses of the hormone. The present experiments were undertaken to assess estradiol-

Male reproductive health and environmental xenoestrogens

Abstract: Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.

Melatonin as an antioxidant: under promises but over delivers.

Abstract: Melatonin is uncommonly effective in reducing oxidative stress under a remarkably large number of circumstances. It achieves this action via a variety of means: direct detoxification of reactive oxygen and reactive nitrogen species and indirectly by stimulating antioxidant enzymes while suppressing the activity of pro-oxidant enzymes. In addition to these well-described actions, melatonin also reportedly chelates transition metals, which are involved in the Fenton/Haber-Weiss reactions; in doing so, melatonin reduces the formation of the devastatingly toxic hydroxyl radical resulting in the reduction of oxidative stress. Melatonin's ubiquitous but unequal intracellular distribution, including its high concentrations in mitochondria, likely aid in its capacity to resist oxidative stress and cellular apoptosis. There is credible evidence to suggest that melatonin should be classified as a mitochondria-targeted antioxidant. Melatonin's capacity to prevent oxidative damage and the associated physiological debilitation is well documented in numerous experimental ischemia/reperfusion (hypoxia/reoxygenation) studies especially in the brain (stroke) and in the heart (heart attack). Melatonin, via its antiradical mechanisms, also reduces the toxicity of noxious prescription drugs and of methamphetamine, a drug of abuse. Experimental findings also indicate that melatonin renders treatment-resistant cancers sensitive to various therapeutic agents and may be useful, due to its multiple antioxidant actions, in especially delaying and perhaps treating a variety of age-related diseases and dehumanizing conditions. Melatonin has been effectively used to combat oxidative stress, inflammation and cellular apoptosis and to restore tissue function in a number of human trials; its efficacy supports its more extensive use in a wider variety of human studies. The uncommonly high-safety profile of melatonin also bolsters this conclusion. It is the current feeling of the authors that, in view of the widely diverse beneficial functions that have been reported for melatonin, these may be merely epiphenomena of the more fundamental, yet-to-be identified basic action(s) of this ancient molecule.

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

Abstract: Melatonin, the major hormone produced by the pineal gland, displays characteristic daily and seasonal patterns of secretion. These robust and predictable rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes in photoperiodic species. In mammals, the nighttime production of melatonin is mainly driven by the circadian clock, situated in the suprachiasmatic nucleus of the hypothalamus, which controls the release of norepinephrine from the dense pineal sympathetic afferents. The pivotal role of norepinephrine in the nocturnal stimulation of melatonin synthesis has been extensively dissected at the cellular and molecular levels. Besides the noradrenergic input, the presence of numerous other transmitters originating from various sources has been reported in the pineal gland. Many of these are neuropeptides and appear to contribute to the regulation of melatonin synthesis by modulating the effects of norepinephrine on pineal biochemistry. The aim of this review is firstly to update our knowledge of the cellular and molecular events underlying the noradrenergic control of melatonin synthesis; and secondly to gather together early and recent data on the effects of the nonadrenergic transmitters on modulation of melatonin synthesis. This information reveals the variety of inputs that can be integrated by the pineal gland; what elements are crucial to deliver the very precise timing information to the organism. This also clarifies the role of these various inputs in the seasonal variation of melatonin synthesis and their subsequent physiological function.

The Regulation of the Mammalian Corpus Luteum

Abstract: Publisher Summary This chapter presents an overview of the regulation of the mammalian corpus luteum (CL) The CL is an ovarian follicle in which the rapid regression—that is otherwise the fate of all postovulatory follicles—is temporarily arrested In the mammalian CL, progesterone secretion goes hand in hand with the postponement of regression It is fairly certain that reptilian CL also secretes progesterone The mammalian CL is formed during the period around ovulation by a transformation of the cells lining the cavity of the follicle Luteinization affects the granulosa cells in all species It involves an enormous enlargement of the cell with a great increase in the nucleus–cytoplasm ratio and the formation of a very distinct cell wall, the development of an extensive capillary network enmeshing all the cells, a marked proliferation of the endoplasmic reticulum, and its transformation from a predominantly rough to a predominantly smooth type, a marked proliferation of the mitochondria from a small round or rod shape type with lamelliform cristae into larger and more varied shapes with tubular and villiform cristae, and an increase in the complexity of the Golgi apparatus The CLs activity differs most from that of the follicle in how much rather than in what kinds of steroid it makes The principal change is a striking increase in progesterone secretion, accompanied by a variable, but severe fall or even loss of the capacity for estrogen and androgen secretion