OBJECTIVES: The current research was conducted to determine whether hyperpolarization-activated c... more OBJECTIVES: The current research was conducted to determine whether hyperpolarization-activated cyclic nucleotide-gated (HCiN1- 4) channels are expressed in gonadotropin-releasing hormone (GnRH) neurons in the female rat hypothalamus and immortalized GnRH neurons (GT1-7 cells). METHODS: Double-label fluorescence immunohistochemistry was used to colocalize HCIN 1-4 channels and GnRH in GnRH neurons in thefemale rat hypothalamus. Reverse transcriptase-polymerase chain reaction (RT-PCR), IWVestern blotting, and immunocytochemistry were used to analyze HC.N channelgene expression in GT1-7 cells. RESULTS: Double-labelfluorescence immunohistochemistry showed that 43 % of hypothalamic GnRH neurons immunostainedfor HCN2 and 90 % of GnRH neurons immunostainedfor HCN,3. RT-PCR and W47estern blot showed expression c(f all four HCIN \ channel subunits in GTI-7 cells. Double-label immunocytochemistry showed cytoplasmic immunostaining of HCI-N2 and HCi\T3 in GT1-7 cells. CONCLUSIONS: This study d...
The ovarian follicle luteinizing hormone (LH) signaling molecules that regulate oocyte meiotic ma... more The ovarian follicle luteinizing hormone (LH) signaling molecules that regulate oocyte meiotic maturation have recently been identified. The LH signal reduces preovulatory follicle cyclic nucleotide levels which releases oocytes from the first meiotic arrest. In the ovarian follicle, the LH signal reduces cyclic nucleotide levels via the CNP/NPR2 system, the EGF/EGF receptor network, and follicle/oocyte gap junctions. In the oocyte, reduced cyclic nucleotide levels activate the maturation promoting factor (MPF). The activated MPF induces chromosome segregation and completion of the first and second meiotic divisions. The purpose of this paper is to present an overview of the current understanding of human LH signaling regulation of oocyte meiotic maturation by identifying and integrating the human studies on this topic. We found 89 human studies in the literature that identified 24 LH follicle/oocyte signaling proteins. These studies show that human oocyte meiotic maturation is regu...
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of ... more Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of proteins within the superfamily of pore-loop cation channels. In mammals, the HCN channel family comprises four members (HCN1-4) that are expressed in heart and nervous system. The current produced by HCN channels has been known as Ih (or If or Iq). Ih has also been designated as pacemaker current, because it plays a key role in controlling rhythmic activity of cardiac pacemaker cells and spontaneously firing neurons. Extensive studies over the last decade have provided convincing evidence that Ih is also involved in a number of basic physiological processes that are not directly associated with rhythmicity. Examples for these non-pacemaking functions of Ih are the determination of the resting membrane potential, dendritic integration, synaptic transmission, and learning. In this review we summarize recent insights into the structure, function, and cellular regulation of HCN channels. We...
Reproductive aging results in declines in female fertility and in slight declines in baseline ser... more Reproductive aging results in declines in female fertility and in slight declines in baseline serum inhibins in humans. The authors tested the hypothesis that exogenous ovarian stimulation as a noninvasive dynamic test, by amplifying inhibin levels, can define more accurately than baseline serum inhibin levels the ovarian age of female rats. Female rats--young (immature, 26 days old), adult (65-75 days old), and reproductively aged (8- to 9-month-old retired breeders)--were administered pregnant mare's serum gonadotropin to stimulate the ovaries and the serum inhibin A and inhibin B, and ovarian inhibins were measured. The young and adult females had at least a 4- to 10-fold increase in serum inhibin A and inhibin B after ovarian stimulation, but the reproductively aged females did not. Adult female serum inhibin measurements after stimulation at every stage of the estrous cycle revealed a consistent 4- to 5-fold increase in all stages, whereas the reproductively aged females did not. Western blot analyses of ovarian lysates were consistent with the serum inhibin level results and revealed that ovarian inhibin alpha, inhibin beta A, and inhibin beta B subunit levels in adult ovaries were elevated after ovarian stimulation but not in the reproductively aged ovaries. The data presented here demonstrate that young, adult, and reproductively aged female inhibin responses after exogenous ovarian stimulation were different. Inhibin measurement in serum after ovarian challenge in rats, therefore, is a noninvasive method that could be used to dissect ovarian function in aging in more detail.
OBJECTIVES: The current research was conducted to determine whether hyperpolarization-activated c... more OBJECTIVES: The current research was conducted to determine whether hyperpolarization-activated cyclic nucleotide-gated (HCiN1- 4) channels are expressed in gonadotropin-releasing hormone (GnRH) neurons in the female rat hypothalamus and immortalized GnRH neurons (GT1-7 cells). METHODS: Double-label fluorescence immunohistochemistry was used to colocalize HCIN 1-4 channels and GnRH in GnRH neurons in thefemale rat hypothalamus. Reverse transcriptase-polymerase chain reaction (RT-PCR), IWVestern blotting, and immunocytochemistry were used to analyze HC.N channelgene expression in GT1-7 cells. RESULTS: Double-labelfluorescence immunohistochemistry showed that 43 % of hypothalamic GnRH neurons immunostainedfor HCN2 and 90 % of GnRH neurons immunostainedfor HCN,3. RT-PCR and W47estern blot showed expression c(f all four HCIN \ channel subunits in GTI-7 cells. Double-label immunocytochemistry showed cytoplasmic immunostaining of HCI-N2 and HCi\T3 in GT1-7 cells. CONCLUSIONS: This study d...
The ovarian follicle luteinizing hormone (LH) signaling molecules that regulate oocyte meiotic ma... more The ovarian follicle luteinizing hormone (LH) signaling molecules that regulate oocyte meiotic maturation have recently been identified. The LH signal reduces preovulatory follicle cyclic nucleotide levels which releases oocytes from the first meiotic arrest. In the ovarian follicle, the LH signal reduces cyclic nucleotide levels via the CNP/NPR2 system, the EGF/EGF receptor network, and follicle/oocyte gap junctions. In the oocyte, reduced cyclic nucleotide levels activate the maturation promoting factor (MPF). The activated MPF induces chromosome segregation and completion of the first and second meiotic divisions. The purpose of this paper is to present an overview of the current understanding of human LH signaling regulation of oocyte meiotic maturation by identifying and integrating the human studies on this topic. We found 89 human studies in the literature that identified 24 LH follicle/oocyte signaling proteins. These studies show that human oocyte meiotic maturation is regu...
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of ... more Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels comprise a small subfamily of proteins within the superfamily of pore-loop cation channels. In mammals, the HCN channel family comprises four members (HCN1-4) that are expressed in heart and nervous system. The current produced by HCN channels has been known as Ih (or If or Iq). Ih has also been designated as pacemaker current, because it plays a key role in controlling rhythmic activity of cardiac pacemaker cells and spontaneously firing neurons. Extensive studies over the last decade have provided convincing evidence that Ih is also involved in a number of basic physiological processes that are not directly associated with rhythmicity. Examples for these non-pacemaking functions of Ih are the determination of the resting membrane potential, dendritic integration, synaptic transmission, and learning. In this review we summarize recent insights into the structure, function, and cellular regulation of HCN channels. We...
Reproductive aging results in declines in female fertility and in slight declines in baseline ser... more Reproductive aging results in declines in female fertility and in slight declines in baseline serum inhibins in humans. The authors tested the hypothesis that exogenous ovarian stimulation as a noninvasive dynamic test, by amplifying inhibin levels, can define more accurately than baseline serum inhibin levels the ovarian age of female rats. Female rats--young (immature, 26 days old), adult (65-75 days old), and reproductively aged (8- to 9-month-old retired breeders)--were administered pregnant mare's serum gonadotropin to stimulate the ovaries and the serum inhibin A and inhibin B, and ovarian inhibins were measured. The young and adult females had at least a 4- to 10-fold increase in serum inhibin A and inhibin B after ovarian stimulation, but the reproductively aged females did not. Adult female serum inhibin measurements after stimulation at every stage of the estrous cycle revealed a consistent 4- to 5-fold increase in all stages, whereas the reproductively aged females did not. Western blot analyses of ovarian lysates were consistent with the serum inhibin level results and revealed that ovarian inhibin alpha, inhibin beta A, and inhibin beta B subunit levels in adult ovaries were elevated after ovarian stimulation but not in the reproductively aged ovaries. The data presented here demonstrate that young, adult, and reproductively aged female inhibin responses after exogenous ovarian stimulation were different. Inhibin measurement in serum after ovarian challenge in rats, therefore, is a noninvasive method that could be used to dissect ovarian function in aging in more detail.
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