Hypothyroidism induced by postnatal PTU (6-n-propyl-2-thiouracil) treatment decreases Sertoli cell number and spermatogenic efficiency in sexually mature pigs.

Studies with 6-n-propyl-2-thiouracil (PTU) in laboratory rodents have shown that transient neonatal hypothyroidism leads to increased Sertoli cell (SC) number, testis size and sperm production. However, scarce and inconclusive data are available for farm animals. In the present study, Piau pigs received PTU in a gel capsule containing 8 mg/kg of body weight for 14 weeks starting from the first week of age, whereas control animals received only the vehicle. Blood samples were collected during the experimental period for hormonal evaluation in the serum. The animals were orchiectomized at adulthood and had their testes used for histomorphometric analysis. Indicating that the PTU concentration used was effective in promoting hypothyroidism, PTU-treated pigs showed a 30% lower body weight and reduced thyroxine levels (p < 0.05) during the treatment period. At adulthood, the body weight was similar in both groups but, surprisingly, PTU-treated pigs showed 30% lower testis weight (p < 0.05). In general, treated pigs presented increased follicle-stimulating hormone levels, whereas testosterone levels tended to be lower from 9 to 23 weeks of age. No significant differences were observed for estradiol, Leydig cell volume and number, tubular diameter, SC number per gram of testis, SC efficiency and meiotic index. However, seminiferous tubule occupancy, total tubular length, SC number per testis, and daily sperm production per testis and per gram of testis (DSP/g/T) were significantly lower (p < 0.05) in PTU-treated pigs. Therefore, in contrast to laboratory rodents, our results showed that SC proliferation and DSP/g/T (spermatogenic efficiency) in Piau pigs is diminished by postnatal PTU treatment.

15 years on the Editorial Board of PEPTIDES.

In this article, part of an issue of PEPTIDES celebrating the many years of dedication of Dr. A.J. Kastin as Editor-in-Chief of the journal, I describe how I first met him and how our friendship and collaboration developed. In 1970 I joined Dr. A.V. Schally's team at the Endocrine and Polypeptide Laboratories of Tulane University and the V.A. Hospital and it was at that time that I met Dr. Kastin for the first time. In 1984 I joined Dr. Schally's team for the second time and I began publishing part of my research findings in PEPTIDES. Afterward many more results from the research work were also published in PEPTIDES. I became a member of the Editorial Board of the same journal in 1999. It was going to be a very interesting experience. Some of my observations as a reviewer for PEPTIDES are described in the present article. Finally, I expressed my warmest congratulations to Dr. A.J. Kastin for the outstanding job that he carried out as Editor-in-Chief of PEPTIDES.

Tachykinins and the hypothalamo-pituitary-gonadal axis: An update.

Tachykinins play a critical role in neuroendocrine regulation of reproduction. The best known members of the family are substance P (SP), neurokinin A and neurokinin B. Tachykinins mediate their biological actions through three G protein-coupled receptors, named NK1, NK2, and NK3. SP was suggested to play an important role in the ovulatory process in mammals and humans. Recent findings suggest a role of tachykinins in the aging of the hypothalamo-pituitary-gonadal axis. A high presence of SP was found in the sheep pars tuberalis and evidence indicates that it may have some role in the control of prolactin secretion. The presence of SP was confirmed in Leydig cells of the rat testes of animals submitted to constant light or treated with estrogens. Tachykinins were found to increase the motility of human spermatozoa. Tachykinins were also found to be present in the mouse ovary and more specifically, in the granulose cells. It is possible that tachykinins may play an important role in the ovarian function. NKB has been implicated in the steroid feedback control of GnRH release. Human mutations in the gene encoding this peptide or its receptor (TACR3) lead to a defect in the control of GnRH. A specific subset of neurons in the arcuate nucleus of the hypothalamus, colocalized three neuropeptides, kisspeptin, NKB and dynorphin. This subpopulation of neurons mediates the gonadal hormone feedback control of GnRH secretion. NKB/NK3 signaling plays a role in puberty onset and fertility in humans. This minireview summarizes the recent data about the action of tachykinins on the hypothalamo-pituitary-gonadal axis.

Role of alpha-melanocyte stimulating hormone and melanocortin 4 receptor in brain inflammation.

Inflammatory processes contribute widely to the development of neurodegenerative diseases. The expression of many inflammatory mediators was found to be increased in central nervous system (CNS) disorders suggesting that these molecules are major contributors to neuronal damage. Melanocortins are neuropeptides that have been implicated in a wide range of physiological processes. The melanocortin alpha-melanocyte stimulating hormone (alpha-MSH) has pleiotropic functions and exerts potent anti-inflammatory actions by antagonizing the effects of pro-inflammatory cytokines and by decreasing important inflammatory mediators. Five subtypes of melanocortin receptors (MC1R-MC5R) have been identified. Of these, the MC4 receptor is expressed predominantly throughout the CNS. Evidence of effectiveness of selective MC4R agonists in modulating inflammatory processes and their low toxicity suggest that these molecules may be useful in the treatment of CNS disorders with an inflammatory component. This review describes the involvement of the MC4R in central anti-inflammatory effects of melanocortins and discusses the potential value of MC4R agonists for the treatment of inflammatory-related disorders.

Tachykinins and the control of prolactin secretion.

Tachykinins are present in the pituitary gland and in brain areas involved in the control of the secretion of pituitary hormones. Tachykinins have been demonstrated to stimulate prolactin release acting directly on the anterior pituitary gland. These peptides have also been revealed to be able to act at the hypothalamic level, interacting with neurotransmitters and neuropeptides that have the potential to affect prolactin secretion. Tachykinins seem to act by stimulating or inhibiting the release of the factors that affect prolactin secretion. Among them, tachykinins have been demonstrated to stimulate oxytocin and vasopressin release, which in turn results in prolactin release. Tachykinins also potentiated the response to vasoactive intestinal peptide (VIP) and reinforced the action of glutamate, which in turn result in prolactin release. They have also been shown to interact with serotonin, a neurotransmitter involved in the control of prolactin secretion. In addition, tachykinins have been shown to inhibit GABA release, a neurotransmitter with prolactin-release inhibiting effect. This inhibition may result in an increased prolactin secretion by removal of the GABA inhibition. On the other hand, tachykinins have also been shown to stimulate dopamine release by the hypothalamus, an action that results in an inhibition of prolactin release. Dopamine is a well known inhibitor of prolactin secretion. In conclusion, although tachykinins have been shown to have a predominantly stimulatory effect on prolactin secretion, especially at the pituitary level, under some circumstances they may also exert an inhibitory influence on prolactin release, by stimulating dopamine release at the hypothalamic level.

Tachykinins and ovarian function in mammals.

Tachykinins are bioactive peptides whose presence has been demonstrated in endocrine glands, where they likely exert a paracrine modulatory activity on hormonal secretions. In the ovary, tachykinins have been shown to be present in nerve fibers, blood vessels, and in granulosa, luteal and interstitial cells. Tachykinin gene expression was shown in granulosa and luteal cells. Tachykinins have also been found in the follicular fluid. Substance P (SP) has been demonstrated to significantly affect the release of hormonal steroids by ovarian cells in vitro. While some authors found that SP stimulated the release of steroids, others found an inhibitory effect by the same tachykinin. Gonadotropins decrease tachykinin concentrations in the ovary. The neonatal treatment of rats with capsaicin, a drug that depletes SP in primary afferent neurons, resulted in a modest reduction in the reproductive success in rats. The experimental results listed in this review suggest that tachykinins are synthesized in the ovary, in the granulosa and luteal cells. Tachykinins are likely intraovarian modulators of the secretion of hormonal steroids. Their stores in the ovary are likely regulated by pituitary gonadotropins.

Tachykinins and their possible modulatory role on testicular function: a review.

Tachykinins are vasoactive and smooth muscle-contracting peptides with widespread localizations. Tachykinins have been localized in the nerve fibres that supply the testes, in the Leydig cells of different animal species, and also in Sertoli cells of the Siberian hamster testes. The presence of substance P (SP) has also been demonstrated in ejaculated human spermatozoa and in the seminal plasma. Tachykinins have been shown to inhibit the release of testosterone by testicular fragments or by isolated Leydig cells in vitro. Acting on Sertoli cells, tachykinins have been shown to stimulate the release of lactate and transferrin by these cells in vitro, and also to stimulate aromatase activity. Leydig and Sertoli cells express the Preprotachykinin A gene, and this fact strongly suggests that tachykinins can be synthesized in the testes. These findings suggest that tachykinins may have a physiological function in the testes as modulators of the functions of the different cell types contained in these organs.

Tachykinins in the normal and gonadotropin-stimulated ovary of the mouse.

In this investigation, substance P (SP) and neurokinin A (NKA) concentrations have been determined in the ovary of control prepubertal mice, and prepubertal mice injected with pregnant mare serum (PMS) gonadotropin, an equine gonadotropin with predominant FSH action, or with PMS followed by human chorionic gonadotropin (hCG), which produces heavily luteinized ovaries after the stimulation with PMS. Control animals were injected with saline. The ovaries of animals treated with gonadotropins were heavier than the control ovaries, the combination of PMS plus hCG produced significantly heavier ovaries than PMS alone. The concentrations of SP and NKA in the ovaries of the animals treated with PMS or PMS/hCG were significantly lower than in control ovaries. No significant differences in ovarian tachykinin concentrations were observed between PMS and PMS/hCG-treated animals. The total ovarian content of SP was lower in PMS-injected animals as compared with the controls. The total ovarian content of NKA was not significantly different in the three groups of animals studied. These results show that ovaries stimulated with gonadotropins have lower concentrations of tachykinins than normal ovaries at the same age. It is therefore evident that gonadotropins can affect tachykinin stores in the ovaries of mice.