Control Of Reproductive Physiology Research Articles

Brain mapping of the gonadotropin-inhibitory hormone-related peptide 2 with a novel antibody suggests a connection with emotional reactivity in the Japanese quail (Coturnix japonica, Temminck & Schlegel, 1849).

Gonadotropin-inhibitory hormone (GnIH) is a neuropeptide first discovered in the quail brain that is involved in the control of reproductive physiology and behaviors, and stress response. GnIH gene encodes a second peptide, GnIH-related peptide-2 (RP2), the distribution and function of which remain unknown. We therefore studied GnIH-RP2 distribution by immunohistochemistry using a novel antibody capable of discriminating between GnIH and GnIH-RP2. The overall distribution of GnIH-RP2 is similar to that of GnIH. The vast majority of labeled neurons is located in the paraventricular nucleus (PVN) of the hypothalamus. Labeling of fibers is conspicuous in the diencephalon, but present also in the mesencephalon and telencephalon. Several regions involved in the control of reproduction and stress response (the PVN, septum, bed nucleus of the stria terminalis and nucleus commissura pallii) showed a dense network of immunolabeled fibers. To investigate the potential function of GnIH-RP2 we compared its expression in two quail lines genetically selected for divergence in their emotional reactivity. A quantitative analysis in the above-mentioned brain regions showed that the density of fibers was similar in the two lines. However, the number of GnIH-RP2 labeled neurons was higher in the median portion of the PVN in birds with higher emotional reactivity. These results point to a possible involvement of GnRH-RP2 in modulating stress response and/or emotional reactivity.

Role of Hormones in the Control of Reproductive Physiology and Reproductive Behavior

In multicellular organisms, intercellular mediators such as hormones or growth factors and morphogens play primary roles in development and reproduction. Evolution of the signaling pathways in which these mediators are involved has thus played an important role in the appearance and success of these species. There are many reproductive modes and behaviours in the animal kingdom. A reproductive behaviour can be defined as all the actions taken by an organism toward the generation of one or more other organism that possesses at least some of its genetic patrimony. From a strict evolutionary point of view, the goal of an organism is to spread its genetic patrimony as much as possible in the next generations of its kind. This egoistic behaviour typically benefits for the entire species since the individuals spreading the most their genetic patrimony is generally those with the best genes and are thus helping their species to be the most fitted possible. In the present review, I briefly describe the implication of hormones in the control of mammals Reproduction and in their Sexual Behavior. In addition, since most multicellular organisms exhibit sexual reproduction, I also take into account hormonal control of reproduction together with sexual behavior.

Artificial insemination in bovine

This literature review aims to show the main scientific advances achieved in the area of Artificial Insemination (AI) within animal reproduction and how these can improve reproductive efficiency and productive of the Brazilian cattle herd. With knowledge of the mechanisms involved in the control of reproductive physiology, in levels endocrine, cellular and molecular, it was possible the development of reproductive biotechnologies, standing out the IA, It has been used on a large scale, by allow the multiplication of animals superior genetically , increase the birthrate and be particularly effective in adjusting the breeding season in cattle. Artificial insemination has an important role in animal genetic improvement; it is the main and more viable middle of spread of genes worldwide when compared to other methods how technologies of embryos and the natural breeding. There are several advantages in using artificial insemination in herd both of cutting as milkman, as herd genetic improvement in lesser time and at a low cost through the use of semen of demonstrably superior sires for production, well as in the control and decrease of diseases which entail reproductive losses and consequently productive, by allowing the creator The crossing of zebuine females with bulls of European breeds and vice-versa, through the use of semen, increasing the number of progeny of a reproducer superior

The amygdala in the guinea pig is sexually dimorphic—A morphometric study

Previous studies have shown that sexual dimorphism in the brain can present two morphological patterns: one in which males present greater morphological measures than females (male>female) and another in which the opposite is true (female>male). These studies have also shown that at least the part of amygdala namely the cortical and medial amygdala, an olfactory region involved in the control of reproductive physiology and behavior, is sexually dimorphic in the rat and other rodents. However, data comparing the basolateral and central amygdala between the sexes is lacking. To my knowledge, the present study is the first morphological work that systematically describes sexual dimorphism throughout the entire amygdala in the guinea pig. The results show that sex differences were found in: (a) the medial amygdala (ME) and its dorsal (MEd) and ventral (MEv) subdivisions, males showing greater values than females in volume and number of neurons, (b) the cortical amygdala (CO) and especially its posterior (COp) subdivision. In the CO, males exhibited a greater number of neurons and in the COp, males showed a greater volume and number of neurons. No differences between the sexes were observed in the basolateral and central amygdala. The results of the present study indicate that in the guinea pig sex differences are present in the large part of the amygdala and they present the male>female pattern, as it was observed in other rodents (rat and hamster), but not in the rabbit. As some previous neurochemical and functional studies have indicated that all parts of the amygdala may be sexually dimorphic, further studies are required to elucidate how much this brain region differs in both sexes.

The control of reproductive physiology and behavior by gonadotropin-inhibitory hormone

Gonadotropin-releasing hormone (GnRH) controls the reproductive physiology and behavior of vertebrates by stimulating synthesis and release of gonadotropin from the pituitary gland. In 2000, another hypothalamic neuropeptide, gonadotropin-inhibitory hormone (GnIH), was discovered in quail and found to be an inhibiting factor for gonadotropin release. GnIH homologs are present in the brains of vertebrates, including birds, mammals, amphibians, and fish. These peptides, categorized as RF amide-related peptides (RFRPs), possess a characteristic LPXRF-amide (X = L or Q) motif at their C-termini. GnIH/RFRP precursor mRNA encodes a polypeptide that is possibly cleaved into three mature peptides in birds and two in mammals. The names of these peptides are GnIH, GnIH-related peptide-1 (GnIH-RP-1) and GnIH-RP-2 in birds, and RFRP-1 and RFRP-3 in mammals. GnIH/RFRP is synthesized in neurons of the paraventricular nucleus of the hypothalamus in birds and the dorsomedial hypothalamic area in mammals. GnIH neurons project to the median eminence, thus providing a functional neuroanatomical infrastructure to regulate anterior pituitary function. In quail, GnIH inhibits gonadal activity by decreasing synthesis and release of gonadotropin. The widespread distribution of GnIH/RFRP immunoreactive fibers in all animals tested suggests various actions within the brain. In accordance, GnIH/RFRP receptor mRNA is also expressed widely in the brain and the pituitary. GnIH/RFRP immunoreactive axon terminals are in probable contact with GnRH neurons in birds and mammals, and we recently demonstrated expression of GnIH receptor mRNA in GnRH-I and GnRH-II neurons in European starlings. Thus, GnIH/RFRP may also inhibit gonadotropin synthesis and release by inhibiting GnRH neurons in addition to having direct actions on the pituitary gland. Intracerebroventricular administration of GnIH/RFRP further inhibits reproductive behaviors in songbirds and rodents, possibly via direct actions on the GnRH system. The expression of GnIH/RFRP is regulated by melatonin which is an internal indicator of day length in vertebrates. Stress stimuli also regulate the expression of GnIH/RFRP in songbirds and rodents. Accordingly, GnIH/RFRP may serve as a transducer of environmental information and social interactions into endogenous physiology and behavior of the animal. Recently, it was shown that GnIH/RFRP and its receptor are also expressed in the gonads of birds, rodents and primates. In sum, the existing data suggest that GnIH/RFRP is an important mediator of reproductive function acting at the level of the brain, pituitary, and the gonad in birds and mammals.

Hormone receptors in the brain and relevance to reproductive aging

The control of reproductive physiology and behavior involves a complex hypothalamic circuitry that both drives, and responds to, gonadal steroid hormones. To determine effects of aging on expression of steroid hormone receptors, we quantified estrogen receptor alpha (ER) and androgen receptor (AR) immunoreactive cells in two key neuroendocrine brain regions: anteroventral periventricular nucleus (AVPV) and medial preoptic nucleus (MPN). Female and male Sprague‐Dawley rats were perfused at young (4 mo), middle‐aged (12 mo) and old (20–24 mo) ages. Females were ovariectomized and treated with estradiol (E2) or vehicle. Male rats were intact. In female rats, numbers of ER cells increased modestly with age in AVPV and MPN, with few effects of hormone treatment. In male rats, AR cell numbers and density increased robustly (3–6x), and ER increased slightly, in both regions during aging. These results are surprising because in females, E2 treatment down‐regulates ER mRNA levels, but we observe little effect of E2 on ER cell numbers, suggesting a disconnect between transcriptional and post‐transcriptional processes. In males, androgen levels decrease with age, but AR immunoreactivity increases dramatically, despite evidence that testosterone up‐regulates its receptors. These results suggest a dysregulation of nuclear receptors in the aging hypothalamus. Funding: AG16765 and AG028051.

Sexual dimorphism in the vomeronasal system of the rabbit

Studies have shown that the vomeronasal system (VNS), an olfactory neural network that participates in the control of reproductive physiology and behavior, is sexually dimorphic in the rat. These works have also shown two main characteristics of brain sexual dimorphism: (a) dimorphism appears in neural networks related to reproduction and (b) it can present two morphological patterns: one in which males present greater morphological measures than females (male > female) and another in which the opposite is true (female > male). The present work extends the hypothesis to the rabbit, as a representative species of Lagomorpha. In addition, the locus coeruleus (LC), which is known to send rich noradrenergic projections to VNS structures, was also studied. Sex differences were found in: (a) the number of mitral, and dark and light granule cells (female > male) of the accessory olfactory bulb (AOB); (b) the medial amygdala (Me) and its dorsal (Med) and ventral (Mev) subdivisions, males showing greater values than females in volume and number of neurons, while in the posteromedial cortical amygdala (PMCo or C 3), females show greater density of neurons than males and (c) the posteromedial division of the bed nucleus of the stria terminalis (BSTMP) in which males have more neurons than females. No sex differences were seen in the bed nucleus of the accessory olfactory tract (BAOT) and the LC. These results evidence that, as it was observed in rodents, sex differences are also seen in the VNS of Lagomorpha and that these sex differences present the two morphological patterns seen in Rodentia. Differences between orders are discussed with respect to the species-specific physiological and behavioral peculiarities.

The relation of serum and follicular fluid leptin and ovarian steroid levels in response to induction of ovulation in in vitro fertilization cycles

Objective: Leptin restores energy homeostasis and regulates appetite and body weight by communicating the energy status to the central nervous system. Although there is strong evidence that leptin affects reproduction, its role in the control of reproductive physiology is little understood. Study design: We studied leptin concentrations in the serum and follicular fluid of 65 women undergoing ovarian hyperstimulation for in vitro fertilization (IVF). Fasting serum samples were collected (1) on the 3rd day of the cycle before IVF and (2) at the time of oocyte retrieval. Serum concentrations of leptin, estradiol (E 2), progesterone, FSH, LH, prolactin, total testosterone, DHEA-SO 4, and TSH and follicular fluid concentrations of leptin, E 2, and progesterone were measured. Results: Serum leptin values increased on average by 66.4% over basal leptin levels on the day of oocyte pick-up (OPU). A positive correlation between leptin increase and body mass index was observed. The serum leptin level was similar to that in follicular fluid o the day of OPU. E 2 levels increased 34.5-fold with controlled ovarian hyperstimulation. There was a negative correlation between the increase in leptin levels and in E 2 levels ( P < 0.05) and in the number of oocytes harvested ( P < 0.05). Conclusion: The significant increase in serum leptin levels during controlled ovarian hyperstimulation indicates a possible role of leptin in reproductive function. The increase in leptin levels is negatively correlated with ovarian response evaluated by E 2 production and number of oocytes retrieved. This might be due to the reduced ovarian response through negative feedback of leptin to the ovaries at high levels.

Expression of proadrenomedullin derived peptides in the mammalian pituitary: co-localization of follicle stimulating hormone and proadrenomedullin N-20 terminal peptide-like peptide in the same secretory granules of the gonadotropes.

Expression of proadrenomedullin-derived peptides in the rat, cow and human pituitary was studied by a variety of techniques. Immunocytochemical detection showed a widespread expression of adrenomedullin peptide in the adenohypophysis and the neural lobe, with low expression in the intermediate pituitary. Proadrenomedullin N-20 terminal peptide (PAMP)-immunoreactivity was also present in the anterior pituitary but showed a more marked heterogeneous distribution, with cells going from very strong to negative immunostaining. Lower levels of PAMP were found in the neural lobe. Interestingly, the distribution of adrenomedullin and PAMP immunoreactivity in the anterior pituitary did not completely overlap. In the present study, we concentrated our efforts to determine which cell type of the adenohypophysis expresses PAMP. Paraffin and semithin serial sections immunostained for PAMP and the classical pituitary hormones revealed that a subpopulation of the gonadotropes expresses high levels of PAMP-immunoreactive material. Ultrastructural analysis clearly showed PAMP-immunoreactivity in the follicle stimulating hormone (FSH)-containing large secretory granules of the gonadotropes, suggesting simultaneous secretion of PAMP and FSH by this cell type. Three mouse adenohypophysis-derived cell lines (AtT20, GH3, and alphaT3-1 derived from corticotropes, lacto/somatotropes and gonadotropes, respectively) were also analysed and showed expression of both proadrenomedullin-derived peptides and their mRNA. Functional studies in these three cell lines showed that neither adrenomedullin nor PAMP was able to stimulate cAMP production in our experimental conditions. Taken together, our results support that proadrenomedullin derived peptides are expressed in the pituitary in cell-specific and not overlapping patterns, that could be explained by differences in postranslational processing. Our data showing costorage of PAMP and FSH in the same secretory granules open a way by which PAMP could be involved in the control of reproductive physiology in a coordinated manner with FSH.

The development of brain sex differences: a multisignaling process

In order to account for the development of sex differences in the brain, we took, as an integrative model, the vomeronasal pathway, which is involved in the control of reproductive physiology and behavior. The fact that brain sex differences take place in complex neural networks will help to develop a motivational theory of sex differences in reproductive behaviors. We also address the classic genomic actions in which three agents (the hormone, the intracellular receptor, and the transcription function) play an important role in brain differentiation, but we also point out refinements that such a theory requires if we want to account of the existence of two morphological patterns of sex differences in the brain, one in which males show greater morphological measures (neuron numbers and/or volume) than females and the opposite. Moreover, we also consider very important processes closely related to neuronal afferent input and membrane excitability for the developing of sex differences. Neurotransmission associated to metabotropic and ionotropic receptors, neurotrophic factors, neuroactive steroids that alter membrane excitability, cross-talk (and/or by-pass) phenomena, and second messenger pathways appear to be involved in the development of brain sex differences. The sexual differentiation of the brain and reproductive behavior is regarded as a cellular multisignaling process.

Serum and follicular fluid leptin during in vitro fertilization: relationship among leptin increase, body fat mass, and reduced ovarian response.

The satiety factor leptin is expressed in several reproductive tissues, but its role in the control of reproductive physiology is not well understood. We studied leptin concentrations in the sera and follicle fluids of 52 women [body fat mass percentage (BFM%) range, 19.6-38.8%] undergoing pituitary down-regulation and ovarian hyperstimulation for in vitro fertilization (IVF) treatment. Fasting serum samples were collected 1) at maximal suppression before the initiation of gonadotropin treatment, 2) at maximal ovarian hyperstimulation, 3) at the time of oocyte retrieval, and 4) 16 days later when all subjects were under exogenous luteal support using 600 mg progesterone daily. Follicular fluid (FF) was obtained at oocyte retrieval from two representative preovulatory follicles in both ovaries. During ovarian hyperstimulation there was a significant 60% increase in serum leptin concentrations from 10.9 +/- 1.1 (SEM) to 15.7 +/- 1.5 ng/mL (P < 0.01) between suppression and maximal hyperstimulation, demonstrating that the ovarian functional state can affect serum leptin concentrations. A serum leptin increase of 22-198% during ovarian hyperstimulation was evident in 43 subjects, whereas in 9, leptin concentrations remained unchanged. A positive correlation between leptin change and BFM% (r = 0.55; P < 0.0005) was observed in the 43 leptin responders. The follicular fluid leptin level was similar to that in serum. In separate linear regression analysis, BFM% contributed to 59-64%, body mass index to 46-56%, and weight to 46-55% (all P < 0.001) of the variability in leptin concentrations at the 4 time points. The 20-fold increase in serum estradiol concentrations during IVF was not significantly correlated with changes in leptin concentrations. On the contrary, the relative serum leptin increase was negatively associated with the ovarian response to hyperstimulation, as revealed by the numbers of follicles (b = -0.28; r2 = 8.1%; P < 0.05) and oocytes retrieved (b = -0.39; r2 = 15.2%; P < 0.01). This relationship was further reflected in a positive correlation between the percent increases in leptin and FSH concentrations (r = 0.39; P < 0.01). The significant relationship of high leptin and reduced ovarian response was also maintained when the cumulative dose of FSH was used as a covariable. Reduced ovarian response was not a function of body mass index, BFM%, basal leptin levels, or insulin concentrations. Fasting serum insulin concentrations remained unchanged in response to IVF, but were positively correlated to serum leptin concentrations at all four time points. Our data suggest that leptin production may be influenced by the ovarian functional state. During IVF a high relative leptin increase is associated with adiposity and a reduced ovarian response. These observations support the possibility that high leptin concentrations might reduce ovarian responsiveness to gonadotropins. Hence, leptin might explain in part why obese individuals require higher amounts of gonadotropins than lean subjects to achieve ovarian hyperstimulation.

Functional Pleiotropy of the Neurohormone Melatonin: Antioxidant Protection and Neuroendocrine Regulation

The pineal hormone melatonin exhibits remarkable functional versatility. Shortly after its discovery, melatonin was functionally linked to the regulation of the neuroendocrine axis, particularly to the reproductive system. However, judging from the wide variety of cellular changes that occurred following either pinealectomy, to remove the primary source of melatonin, or the exogenous administration of the indole, it was obvious that the activity of melatonin far transcended its actions on the hypothalamo-pituitary-gonadal system. Roughly 30 months ago it was discovered that melatonin is a highly efficient free radical scavenger and general antioxidant. This implied that melatonin, which is both lipophilic and hydrophilic, has effects not only in every cell but also within every subcellular compartment. These intracellular actions of melatonin, some of which are independent of any receptor interaction and some of which are mediated by nuclear receptors, have become the focus of much of the current investigation. As an antioxidant, melatonin has been shown in vitro to be a highly efficient scavenger of the very reactive and toxic hydroxyl radical. Indeed, on an equimolar basis melatonin proved significantly more efficient in neutralizing the hydroxyl radical than did the two well-known scavengers, glutathione and mannitol. Likewise, melatonin was found to also scavenge the peroxyl radical which is generated during lipid peroxidation; in this regard it was roughly twice as effective as vitamin E (α-tocopherol). The antioxidant activities of melatonin have been well documented in tissue homogenates and organisms as well. When rats are treated with the chemical carcinogen safrole, this agent induces the generation of free radicals which in turn extensively damage nuclear DNA; this damage is almost totally eliminated if the animals are cotreated with melatonin. Also, damage to DNA in human lymphocytes due to ionizing radiation, another treatment which is known to induce free radical formation, is greatly reduced if the cells are treated with melatonin prior to radiation. Cytosolic protein seems also to be protected from free radical damage when melatonin is present. When newborn rats are treated with a glutathione-depleting drug at birth, by 2 weeks of age the animals have cataracts. Cataracts form because oxidants damage protein in the presence of low intracellular levels of glutathione. Cataracts induced by this means are essentially prevented if the glutathione-depleted rats are supplemented with melatonin. Finally, membrane lipid peroxidation, induced either in vivo or in vitro by any of several means, all of which involve free radicals, is drastically attenuated in the presence of melatonin. Considering melatonin's ability to cross all morphophysiological barriers and to enter every cell, and all subcellular compartments, the implication is that this indole may play a very important role in the antioxidative defense system of the organism. These findings potentially have important implications for a wide variety of age-related diseases and to aging itself. Melatonin's control of reproductive physiology in photoperiodic mammals is well documented. However, the site of interaction of melatonin with the neuroendocrine axis has been especially difficult to determine. The discovery and cloning of a membrane melatonin receptor on neurosecretory cells in the hypothalamus and on hormone secreting cells of the anterior pituitary gland stimulated a great deal of investigation which has failed to prove the involvement of these receptors in the processes by which melatonin influences reproductive physiology. The recent identification of nuclear melatonin receptors as well as the nonreceptor-mediated actions of the indole are currently being examined as to their association with reproductive function.

Neuroendocrine effects of light

The light/dark cycle to which animals, and possibly humans, are exposed has a major impact on their physiology. The mechanisms whereby specific tissues respond to the light/dark cycle involve the pineal hormone melatonin. The pineal gland, an end organ of the visual system in mammals, produces the hormone melatonin only at night, at which time it is released into the blood. The duration of elevated nightly melatonin provides every tissue with information about the time of day and time of year (in animals that are kept under naturally changing photoperiods). Besides its release in a circadian mode, melatonin is also discharged in a pulsatile manner; the physiological significance, if any, of pulsatile melatonin release remains unknown. The exposure of animals including man to light at night rapidly depresses pineal melatonin synthesis and, therefore, blood melatonin levels drop precipitously. The brightness of light at night required to depress melatonin production is highly species specific. In general, the pineal gland of nocturnally active mammals, which possess rod-dominated retinas, is more sensitive to inhibition by light than is the pineal gland of diurnally active animals (with cone-dominated retinas). Because of the ability of the light/dark cycle to determine melatonin production, the photoperiod is capable of influencing the function of a variety of endocrine and non-endocrine organs. Indeed, melatonin is a ubiquitously acting pineal hormone with its effects on the neuroendocrine system having been most thoroughly investigated. Thus, in nonhuman photoperiodic mammals melatonin regulates seasonal reproduction; in humans also, the indole has been implicated in the control of reproductive physiology.

Evaluation of extrahypothalamic control of reproductive physiology.

Extrahypothalamic areas such as amygdala, hippocampus, and midbrain are anatomically and functionally closely connected to the mediobasal hypothalamus, which is held responsible for the secretion of releasing factors controlling anterior pituitary-gonadal function. Experimental evidence clearly assigns a role to limbic structures for the onset of puberty. In both immature and adult female and male individuals, limbic and midbrain areas concentrate gonadal steroids which can be related to reproductive physiology. Likewise, it is possible to alter pituitary hormone secretion by changing activities of the limbic midbrain circuit, or associate electrical activity of these brain areas with reproductive patterns. However, we are still confronted with our ignorance on why changes are brought about and how systems like the limbic midbrain circuit are interacting.