Category Archives: Reproductive Axis

Leptin’s Actions on the Reproductive Axis: SUMMARY(2)


Leptin treatment restores estrous cyclicity in fasted animals, but not in animals that have also received injections of 2-deoxyglu-cose. This implies that leptin’s effects on reproduction may be due to its influence on metabolic fuel availability, and that leptin acts to provide signals to glucose-sensitive regions of the brain, which then influence GnRH secretion. Cheap Diskus Advair

Leptin’s Actions on the Reproductive Axis: SUMMARY(1)

The facts presently available support the hypothesis that leptin plays an important role in relaying energetic status to the reproductive axis; however, the mechanisms subserving leptin’s effects in this context remain elusive. While the presence of Ob-R in the ventral forebrain is tantalizing, there is as yet no conclusive evidence that leptin directly influences the activity of GnRH-containing neurons. If one proposes that leptin acts indirectly to affect GnRH secretion, several possible modes of action are conceivable. Lep-tin may positively or negatively influence the synthesis and/ or secretion of other hypothalamic peptides (e.g., POMC gene products, NPY, corticotropin-releasing hormone, gal-anin), which then in turn modulate GnRH release (Fig. 3). Buy Advair Diskus Online

Leptin’s Actions on the Reproductive Axis: MECHANISMS OF LEPTIN’S ACTIONS ON REPRODUCTION(5)


Thus the potential exists for leptin to influence reproductive function during fasting through altering the availability of POMC gene products. Indeed, the endogenous opioid p-endorphin as well as a-melanocyte-stimulating hormone (a-MSH) have been implicated in modulating both feeding and reproduction. If leptin-induced changes in р-endorphin transmission influence GnRH secretion, it may be through indirect means, as GnRH neurons are believed to lack the classical opioid receptor subtypes (^, к, and 8). Leptin’s inhibitory actions on food intake are thought to be due, in part, to signaling through hypothalamic melanocortin type 4 (MC4) receptors, for which a-MSH (among other POMC gene products) is an endogenous ligand. However, experiments demonstrating the involvement of MC4 receptors in transducing leptin’s stimulatory effects on reproductive parameters using specific MC4 agonists/antagonists have not yet been published. ampicillin antibiotic

Leptin’s Actions on the Reproductive Axis: MECHANISMS OF LEPTIN’S ACTIONS ON REPRODUCTION(4)

Other substances may be intermediaries in the signal transduction pathway between leptin and GnRH release. Neurons containing products of the proopiomelanocortin (POMC) gene (e.g., (3-endorphin, adrenocorticotropic hormone) make direct synaptic contacts with GnRH-containing neurons, and are found in the Arc, a region of high expression of Ob-R mRNA. Using double-label in situ hybridization, we have demonstrated a high coincidence of expression of both POMC and Ob-R mRNAs in the Arc of both rats and monkeys (Fig. 2B), while Hakims-son et al. have shown colocalization of Ob-R and adrenocorticotropic hormone immunoreactivity in the Arc of the rat. antibiotics levaquin

Leptin’s Actions on the Reproductive Axis: MECHANISMS OF LEPTIN’S ACTIONS ON REPRODUCTION(3)


Although distribution of Ob-R in the brain varies among those species studied thus far (for discussion see ), all species to date express Ob-R mRNA in the arcuate (Arc) and ventromedial nuclei (VMN) of the hypothalamus (Fig. 2A)—two areasacknowledgedtoinfluencebothfeeding and reproductive behaviors. To elucidate the neuronal pathways by which leptin influences reproductive function, we and others have begun to identify the phenotypes of neurons that are responsive to leptin (i.e., express Ob-R) through double-labeling experiments, using both in situ hybridization and immunohistochemistry. antibiotic levaquin

Leptin’s Actions on the Reproductive Axis: MECHANISMS OF LEPTIN’S ACTIONS ON REPRODUCTION(2)

Distribution of Ob-R and its mRNA has been examined in several species, including the mouse, rat, monkey, and human. The Ob-R has been found at all points along the HPG axis. Several groups have documented evidence of Ob-R mRNA in the gonads of mice, rats, and humans. Leptin has been shown to regulate expression of mRNAs for side chain cleavage enzyme and 17a-hydroxylase and to modulate LH-stimulated estradiol production in the ovary, providing evidence of functional Ob-R in these tissues. buy cheap antibiotics

Leptin’s Actions on the Reproductive Axis: MECHANISMS OF LEPTIN’S ACTIONS ON REPRODUCTION(1)


Leptin would appear to play a role in relaying metabolic information to the reproductive axis, but the mechanism(s) by which this is accomplished remains unknown. The search for sites of leptin’s action began with the cloning of its receptor (Ob-R) in mice and humans. The Ob-R is a single-pass membrane receptor of the class I cytokine receptor family (reviewed in ). Multiple splice variants have been found, which have identical extracellular domains and either a long (~300 amino acids) or short (~30 amino acids) intracellular domain. Stimulation of the long form activates signal transducer and activator of transcription (STAT) proteins both in vivo and in vitro, whereas the short form is apparently incapable of signaling via this pathway. birth control yasmin

Leptin’s Actions on the Reproductive Axis: LEPTIN AND THE ONSET OF PUBERTY(4)

Is leptin the primary signal to awaken the reproductive system at puberty? The ability of exogenous leptin to initiate puberty prematurely would seem to strengthen support for the ‘‘critical body fat’’ hypothesis of sexual development. Two studies demonstrate an advancement of pubertal onset in female mice by leptin treatment. Chehab et al. treated mice beginning on postnatal Day 21 with daily i.p. injections of leptin (2 ^g/g BW) or PBS. Leptin-treated animals showed 1-4 days advancement of VO, increased reproductive organ (uteri, ovaries, oviducts) weights, and decreased latency to first mating compared to PBS-treated animals. However, a footnote to this study states that the authors had difficulty replicating their observation of a leptin-induced advancement of VO. buy flovent inhaler

Leptin’s Actions on the Reproductive Axis: LEPTIN AND THE ONSET OF PUBERTY(3)


Circulating leptin levels have been measured over development in several species. In female mice, a peak in plasma levels of leptin during the second week of postnatal life has been reported, which occurs independently of changes in body weight and before the developmental increase in estradiol. Gruaz et al. examined plasma leptin levels in female rats between postnatal Days 24 and 59 (average age of VO approximately Day 40) and observed a steady rise in leptin levels in proportion to body weight over the sampling period, although one cannot discount the possibility of a peak occurring before Day 24. Studies in male rhesus macaques show little change in leptin levels over the peripubertal period, when LH, FSH, and testosterone levels begin to climb to adult levels. buy yasmin online

Leptin’s Actions on the Reproductive Axis: LEPTIN AND THE ONSET OF PUBERTY(2)

At 43 days of age, only 5 of 8 leptin-treated animals had shown VO, and 4 of 8 showed first estrus, whereas all ad lib-fed animals and no pair-fed animals had experienced these events. Thus, artificially elevated leptin levels may be insufficient to reverse the delay of pubertal onset that comes with food deprivation—ggugg thatleptin by itself cannot trigger the changes in GnRH secretion required to initiate puberty. buy ventolin inhalers

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