Biomedical subjects

K Scarbrough

Publications and source records attributed to K Scarbrough.

At least 19 recordsLinked to original sources

PubMed2000

Use of antisense oligodeoxynucleotides to study biological rhythms.

Perturbation analysis has been crucial in the study of biological rhythms. Antisense technology provides investigators with new means to alter the internal milieu of the circadian clock itself. Practical aspects of the method and the theoretical background are presented in sufficient detail to enable others to design appropriate antisense oligodeoxynucleotides and use them for research purposes. This strategy will contribute substantially to the understanding of the influence of individual genes on rhythms in hormone secretion, metabolism, and behavior.

Animals↗

PubMed2000

Locomotor response to an open field during C57BL/6J active and inactive phases: differences dependent on conditions of illumination.

Time of day has proven to be a source of variability in diverse behavioral measures. Knowledge of the pattern of this temporal effect as well as its origin (exogenous or endogenous) is essential for a precise description of any behavior. This study analyzed the effect of the external light-dark cycle and the internal rest-activity rhythm on the response of C57BL/6J mice to a novel environment. In a first experiment, animals maintained in a 12:12-h light-dark cycle were tested in an open field at six different times of day. A diurnal rhythm of ambulation in the open field was observed with greater levels of activity exhibited by those groups tested at night. Long-term and short-term behavioral habituation to spatial novelty were also affected by phase of the light-dark cycle. A second experiment was designed to control for any direct effect of the light-dark cycle by keeping the animals in dim green light where entrainment was maintained by a skeleton photoperiod (two 15-min bright-light pulses separated by 12 hours of green, dim light). This second group of animals was tested at two different circadian phases under the same conditions of illumination. One group was tested during the subjective night and another group during the subjective day, i.e., 2 or 14 h after the onset of the active phase, as assessed by wheel-running behavior. No effect of circadian phase on ambulation or habituation of this response to the open field was observed in these animals. Taken together, these results suggest that spatial novelty is equally arousing regardless of circadian phase and that the conditions of illumination can dramatically alter the response to a novel environment.

Animals↗

PubMed1999

Using variability to regulate long term biological rhythms.

We present a model for the generation of precise, long term rhythms from a collection of imprecise, short term oscillators. The model uses variability between oscillators in conjunction with simple coupling rules to produce long term rhythms that are independent of rate equations (e.g. Arrhenius). The rhythms generated by the model are controlled by only two independent parameters and exhibit several physiologically interesting properties, including ready entrainment to external signals and splitting in response to strong constant signals. The model provides several predictions that can be tested in future experiments.

Animals↗

PubMed1998

Roles of suprachiasmatic nuclei and intergeniculate leaflets in mediating the phase-shifting effects of a serotonergic agonist and their photic modulation during subjective day.

Serotonin (5-HT) has been implicated in the phase adjustment of the circadian system during the subjective day in response to nonphotic stimuli. Two components of the circadian system, the suprachiasmatic nucleus (SCN) (site of the circadian clock) and the intergeniculate leaflet (IGL), receive serotonergic projections from the median raphe nucleus and the dorsal raphe nucleus, respectively. Experiment 1, performed in golden hamsters housed in constant darkness, compared the effects of bilateral microinjections of the 5-HT1A/7 receptor agonist, 8-hydroxydipropylaminotetralin (8-OH-DPAT; 0.5 microgram in 0.2 microliter saline per side), into the IGL or the SCN during the mid-subjective day. Bilateral 8-OH-DPAT injections into either the SCN or the IGL led to significant phase advances of the circadian rhythm of wheel-running activity (p < .001). The phase advances following 8-OH-DPAT injections in the IGL were dose department (p < .001). Because a light pulse administered during the middle of the subjective day can attenuate the phase-resetting effect of a systemic injection of 8-OH-DPAT, Experiment 2 was designed to determine whether light could modulate 5-HT agonist activity at the level of the SCN and/or the IGL. Serotonergic receptor activation within the SCN, followed by a pulse of light (300 lux of white light lasting 30 min), still induced phase advances. In contrast, the effect of serotonergic stimulation within the IGL was blocked by a light pulse. These results indicate that the respective 5-HT projections to the SCN and IGL subserve different functions in the circadian responses to photic and nonphotic stimuli.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1997

Acoustic assessment of the physical integrity of Björk-Shiley convexo-concave heart valves.

BACKGROUND: Several lines of evidence indicate a two-stage failure mode for the Björk-Shiley convexo-concave (C/C) heart valve, in which one of the two outlet strut legs separates from the flange before the other, potentially providing an opportunity to identify and prophylactically replace failure-prone valves. Radiographic single leg separation (SLS) detection, although successful, is subjective and skill intensive, implying a need for both an objective preliminary screen and subsequent corroboration of the radiographic findings. METHODS AND RESULTS: We developed a time-windowed, power density analysis of C/C valve closing sounds to detect the vibrational resonance that characterizes the presence of an intact outlet strut in clinically functioning, 29-mm-flange size C/C valves. Recordings from more than 800 patients enrolled in radiographic SLS detection studies were analyzed, and the assessment algorithm was evaluated through a blinded test of 32 study valves for which the true status became known consequent to an autopsy or surgical explantation. Valves were objectively scored on a 0-to- 1 scale, with 1 being assuredly intact and scores of < 0.50 indicating a probable SLS. All except five valves (incorrectly designated probable SLS) were classified correctly, for a sensitivity of 1.00 (95% confidence interval, 0.79 to 1.00) and a specificity of 0.69 (0.41 to 0.89). CONCLUSIONS: This level of accuracy is sufficient to serve as an effective preliminary screen, potentially allowing a threefold concentration of SLS prevalence among the C/C valves of patients undergoing radiographic assessment. The value of acoustic classification in avoiding unnecessary operations prompted by false-positive radiographs is less certain.

Acoustics↗

PubMed1997

Aging and photoperiod affect entrainment and quantitative aspects of locomotor behavior in Syrian hamsters.

Aging affects the regulation of diurnal and circadian rhythmicity. We tested the hypothesis that the age-related difference in the phase angle of entrainment of the locomotor activity rhythm to a light-dark (LD) cycle would be greater under LD 6:18 than LD 14:10. We also analyzed changes in quantitative aspects of wheel-running behavior according to age group. Young (9-wk-old), middle-aged (11- to 12-mo-old), and old (15- to 17-mo-old) male golden hamsters were entrained to a 14:10 LD cycle followed by re-entrainment to a 6:18 LD cycle. Fourteen days after the start of locomotor recording in LD 14:10 and again after 27 days in LD 6:18, the phase of activity onset, the total number of wheel revolutions performed per day, the peak intensity of wheel-running activity, the duration of the active period, and the level of fragmentation of locomotor activity were quantitated. We also studied the temporal distribution of the largest bout of wheel-running activity among the age groups in both photoperiods. Short days induced testicular regression at a similar rate among young, middle-aged, and old hamsters. The data are discussed in terms of the effects of age on overall circadian organization in the seasonally changing environment.

Aging↗

PubMed1997

Fetal grafts containing suprachiasmatic nuclei restore the diurnal rhythm of CRH and POMC mRNA in aging rats.

We assessed whether fetal tissue containing the suprachiasmatic nuclei (SCN) can restore age-related changes in the diurnal rhythm of hypothalamic corticotropin-releasing hormone (CRH) and anterior pituitary proopiomelanocortin (POMC) mRNA. Young, middle-aged, and middle-aged SCN-transplanted rats were killed at seven times of day. In young rats, CRH mRNA exhibited a diurnal rhythm in the dorsomedial paraventricular nuclei but not in other subdivisions of the nuclei. No rhythm was detected in aging rats. SCN transplants restored a rhythm in CRH mRNA, but the timing was not precisely the same as in young animals. POMC mRNA exhibited a daily rhythm in young rats. Aging abolished the rhythm and decreased the average mRNA level; fetal transplants restored the rhythm, but the amplitude remained attenuated. These data are the first demonstration that fetal tissue can restore the diurnal rhythm of a neuroendocrine axis that is driven by the SCN. We conclude that the neuroendocrine substrate from the aging host remains capable of responding to diurnal cues to express diurnal rhythmicity in CRH/POMC mRNA when fetal SCN transplants confer the appropriate signals.

Aging↗

PubMed1997

Effects of aging on the circadian rhythm of wheel-running activity in C57BL/6 mice.

The effects of age on the circadian clock system have been extensively studied, mainly in two rodent species, the laboratory rat and the golden hamster. However, less information is available on how aging alters circadian rhythmicity in a commonly studied rodent animal model, the mouse. Therefore, in the present study we compared the rhythm of wheel-running activity in adult (6-9 mo) and old (19-22 mo) C57BL/6J mice maintained under different lighting conditions for a period of 4 mo. During this period, mice were subjected to phase advances and phase delays of the light-dark (LD) cycle and eventually to constant darkness (DD). In LD (12 h light, 12 h dark), old mice exhibited delayed activity onset relative to light offset and an increase in the variability of activity onset compared with adult mice. After a 4-h phase advance of the LD cycle, old mice took significantly longer to reentrain their activity rhythm when compared with adult animals. Old mice also demonstrated a decline in the number of wheel revolutions per day and a tendency toward a decrease in the length of the active phase. An increase in fragmentation of activity across the 24-h day was obvious in aging animals, with bouts of activity being shorter and longer rest periods intervening between them. No age difference was detected in the maximum intensity of wheel-running activity. In DD, the free-running period was significantly longer in old mice compared with adults. In view of the rapidly expanding importance of the laboratory mouse for molecular and genetic studies of the mammalian nervous system, the present results provide a basis at the phenotypic level to begin to apply genetic methods to the analysis of circadian rhythms and aging in mammals.

Aging↗

PubMed1997

Rapid photoperiod-induced increase in detectable GnRH mRNA-containing cells in Siberian hamster.

To determine whether changes in gonadotropin-releasing hormone (GnRH) neurons are early indicators of photostimulation, Siberian hamsters were placed in short days (6:18-h light-dark) at 3 (experiment 1) or 6 (experiment 2) wk of age where they were held for 3 (experiment 1) or 4 (experiment 2) wk. Hamsters were then moved to long photoperiod (16:8-h light-dark). In experiment 1, brains were collected 1-21 days after transfer from short to long days. In experiment 2, brains were collected only on the second morning of long day exposure. Long and short day controls were included in both experiments. Cells containing GnRH mRNA, as visualized by in situ hybridization, were counted. As expected, there were no differences in the number of detectable GnRH mRNA-containing cells among animals chronically exposed to long or short photoperiods. However, on the second morning after transfer from short to long photoperiod, a positive shift in the distribution of GnRH mRNA-containing cells occurred relative to the respective controls in the two experiments. Increases in follicle-stimulating hormone secretion and gonadal growth occurred days later. In conclusion, a rapid but transient increase in the distribution of detectable GnRH mRNA-containing cells is an early step in the photostimulation of the hypothalamic-pituitary-gonadal axis.

Animals↗

PubMed1997

Aging of the female reproductive system: a window into brain aging.

The menopause marks the permanent end of fertility in women. It was once thought that the exhaustion of ovarian follicles was the single, most important explanation for the transition to the menopause. Over the past decade, this perception has gradually changed with the realization that there are multiple pacemakers of reproductive senescence. We will present evidence that lends credence to the hypothesis that the central nervous system is a critical pacemaker of reproductive aging and that changes at this level contribute to the timing of the menopause. Studies demonstrate that an increasing de-synchronization of the temporal order of neuroendocrine signals may contribute to the accelerated rate of follicular loss that occurs during middle age. We suggest that the dampening and destabilization of the precisely orchestrated ultradian, circadian, and infradian neural signals lead to miscommunication between the brain and the pituitary-ovarian axis. This constellation of hypothalamic-pituitary-ovarian events leads to the inexorable decline of regular cyclicity and heralds menopausal transition.

Aged↗

PubMed1996

Quantitative differences in the circadian rhythm of locomotor activity and vasopressin and vasoactive intestinal peptide gene expression in the suprachiasmatic nucleus of tau mutant compared to wildtype hamsters.

The activity profiles of homozygous tau mutant hamsters bred in our colony exhibit several differences when compared to wildtype golden hamsters. In addition, tau mutant hamsters respond to saturating white light pulses presented between circadian time (CT) 11 and CT 16 with extremely large phase shifts (type 0 resetting) after prolonged time in constant darkness. We measured five parameters of the activity rhythm early during exposure to constant darkness (DD) (cycles 5-9), and after 44-48 cycles in DD, and we confirmed the tau mutants' unusual phase shifting response to light. Next we determined whether neurotransmitter peptide mRNA levels in the SCN differed between wildtype and tau mutant hamsters exhibiting these divergent activity patterns and responses to light. After 49 circadian cycles in DD, tau mutant hamsters responded to a 1 h light pulse at CT 15 with phase shifts averaging 10.19 +/- 0.35 h. Among wildtype hamsters the mean phase shift was 1.22 +/- 0.34 h and the largest phase shift observed was 3.67 h. Total wheel revolutions/circadian cycle were significantly lower in tau mutants (4022 +/- 1103) vs. wildtypes (7528 +/- 458) and there was a significant decrease in wheel-running activity after prolonged exposure to DD, particularly among the wildtype hamsters (tau = 3045 +/- 972, wildtype = 4362 +/- 388 rev/circadian cycle). When analyzed by 5 min segments throughout the circadian cycle, the highest intensity wheel-running activity did not differ between groups and there was no significant effect of length of time in DD on this measure (tau = 38.5 +/- 6.3 and 38.4 +/- 4.7 rev/min, wildtype = 46.8 +/- 1.7 and 41.4 +/- 2.7 rev/min early or late in DD, respectively). The precision of activity onset differed greatly between groups with tau mutants exhibiting a much higher daily deviation from mean tau (1.00 +/- 0.24 h) than wildtypes (0.14 +/- .02 h). Activity onset became significantly less precise with increased time in DD: tau = 1.66 +/- 0.21 h, wildtype = 0.45 +/- 0.14 h after 44-48 circadian cycles. The length of the active period, alpha, was significantly shorter in tau mutants than in wildtypes (7.2 +/- 0.2 h vs. 8.0 +/- 0.2 h) but alpha was a similar percentage of tau in the two groups (tau mutant = 36%, wildtype = 33%). After 48 circadian cycles in DD, alpha measured 7.2 +/- 0.5 h in tau mutants and 8.9 +/- 0.6 h in wildtypes, thus there was no significant effect of time in DD on this parameter. Activity records of tau mutant animals appear more fragmented to the eye and we quantitated this with a computer-aided analysis of the number of bouts of wheel-running per active period. Wildtype hamsters exhibited 2.8 +/- 0.2 bouts of wheel-running activity early in DD and 3.1 +/- 0.2 bouts per circadian cycle later in DD. The activity records of tau mutant hamsters were significantly more fragmented but this group actually showed some consolidation of bouts per circadian cycle after prolonged time in DD (4.7 +/- 0.3 vs. 3.9 +/- 0.3 bouts per cycle). Wildtype and tau mutant hamsters were killed after 66-71 cycles in DD at either CT 4 or CT 16 and in situ hybridization was performed for vasopressin (AVP) and vasoactive intestinal peptide (VIP). Levels of AVP and VIP mRNA were significantly lower in tau mutant than wildtype hamsters at CT 16. We conclude that the tau mutation causes these differences in gene expression and we speculate that differences in the peptidergic output of the clock may have some relevance for the differences in the quantitative aspects of the activity rhythm and the response to light pulses exhibited by these animals.

Animals↗

PubMed1996

Acute effects of antisense antagonism of a single peptide neurotransmitter in the circadian clock.

The circadian clock that resides in the suprachiasmatic nucleus (SCN) of the hypothalamus is the major neural pacemaker driving most 24-h rhythms in mammals. Several neurotransmitter peptides are synthesized within this nucleus and communicate rhythmically with other cells in the SCN as well as with cells in other regions of the brain. At the present time, little is known about their role in regulating outputs of the clock. We demonstrate that antisense oligodeoxynucleotides corresponding to the NH2-terminus and the translation start site of vasoactive intestinal peptide (VIP) mRNA infused into the suprachiasmatic region of rats temporarily abolishes the circadian rhythm of corticosterone secretion without influencing stress-related corticosterone secretion in the same animals. Levels of VIP peptide are suppressed 30% on the second day after antisense treatment. These results indicate that a single neuropeptide transmitter in the circadian clock may serve a distinct role in the control of specific circadian rhythms.

Animals↗

PubMed1996

In vivo antisense antagonism of vasoactive intestinal peptide in the suprachiasmatic nuclei causes aging-like changes in the estradiol-induced luteinizing hormone and prolactin surges.

In mammals, the suprachiasmatic nuclei (SCN) regulate the timing of LH surges. Recent evidence suggests that vasoactive intestinal peptide (VIP), an abundantly expressed neuropeptide of the SCN, communicates time of day information from the SCN to GnRH neurons. VIP levels in the SCN decrease with age and may be responsible for alterations in LH surges that become apparent in middle-aged rats. We wished to determine whether suppression of VIP synthesis, through antisense oligonucleotides (oligos) directed at the SCN, results in 1) selective suppression of VIP levels in the SCN and 2) aging-like changes in the secretion of LH and PRL. To test the specificity of antisense oligo treatment, rats were ovariectomized and treated with estradiol. Antisense or control random oligos were infused into the peri-SCN region through stereotaxically placed bilateral cannulas. Beginning at lights off, rats were maintained in constant dim red illumination throughout the remainder of the experiment. They were killed at specific times, brains were microdissected, and VIP concentrations in the SCN, paraventricular nuclei, and cortex were assayed. As a control for the specificity of antisense VIP treatment, we monitored the levels of arginine vasopressin in the SCN. To test the effects of antisense treatment on the pattern of plasma LH and PRL secretion, blood samples were collected from atrial catheters from 1200-2000 h, and plasma samples were assayed for LH and PRL. The results indicate that the effects of antisense treatment were discrete, as they suppressed VIP concentrations in the SCN, but had no effect on VIP concentrations in the paraventricular nuclei or cortex or on arginine vasopressin concentrations in the SCN. Peak LH levels during the surge were delayed and attenuated in antisense-treated animals compared to random oligo-treated control rats in a manner strikingly similar to that observed previously in middle-aged rats. Likewise, PRL, which was unaffected in middle-aged rats, was also unaffected by targeted suppression of VIP. In summary, our findings clearly demonstrate that antisense VIP oligos suppress VIP levels in the SCN and do not affect peptide concentrations in other regions of the brain or other neuropeptides in the SCN. Further, we show that suppression of a single neuropeptide in the SCN can mimic the effects of age on the estradiol-induced surges of LH and PRL. These data support a central role for suprachiasmatic VIP in the regulation of the LH surge and suggest that age-related perturbations in the integrity of this axis may account for alterations in the pattern of LH secretion observed during middle age.

Aging↗

PubMed1994

Photoperiod regulates testis cell apoptosis in Djungarian hamsters.

Reproductive activity in the Djungarian hamster is controlled by seasonal variations in day length. Exposure to long days stimulates testis development, while exposure to short days induces testis regression. We recently found that testis regression after gonadotropin deprivation in rats is associated with increases in apoptosis. Here we sought to determine whether or not apoptosis is associated with the testis regression and/or recrudescence that occurs naturally in seasonally breeding mammals. Newborn male hamsters were maintained on long days (16L:8D) until 3 wk of age before being transferred to short days (8L:16D). Following decreases in serum FSH within 3 days of exposure to short days, testis weight decreased by 52% at Day 10, reaching a 70% decrease after 21 days. Analysis of testis cell DNA fragmentation showed a 4.9-fold increase of low-molecular-weight DNA as early as 5 days after transfer to short days; this was followed by a time-dependent decrease. The observed increases in testis cell apoptosis were correlated with decreases in serum testosterone, but decreases in Leydig cell LH receptor content were delayed. In a second study, 6-wk-old hamsters with regressed testes due to a 3-wk exposure to short days were transferred back to long days. After increases in serum FSH within 3 days of photostimulation, a 2-fold elevation in testis weight was found at Day 5. The increase in testis weight was associated with a 65% decrease of testis apoptosis within 5 days of photostimulation. Also, increases in serum testosterone and LH receptor content were observed after 5 and 10 days of exposure to long days, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

The effect of time of day on levels of hypothalamic proopiomelanocortin primary transcript, processing intermediate and messenger ribonucleic acid in proestrous and estrous rats.

Several lines of evidence from different laboratories suggest that hypothalamic beta-endorphinergic activity decreases around the time of initiation of the LH surge and may increase on estrus to extinguish the expression of the daily neuronal signal for the surge. In several hormone systems, factors that stimulate or suppress hormone release also stimulate or repress transcription of the hormone gene and translation of the messenger RNA encoding the hormone. Therefore, information about neurohormone activity may be inferred from data on changes in the levels of RNA species encoding these neurohormones. We used a solution hybridization/RNase protection assay to test the hypotheses that 1) the abundance of primary transcript of the hypothalamic POMC gene decreases at the time of initiation of the proestrous LH surge and 2) levels of POMC primary transcript (and by inference, levels of beta-endorphin neuronal activity and secretion) increase on estrus. 96 rats exhibiting at least two consecutive 4-day estrous cycles were killed at either 0600 or 1300 h on proestrus and estrus. Dissections of the medial basal hypothalamus were pooled into 4 samples at each time-point (6 rats per sample) and RNA was extracted from nuclear and cytoplasmic fractions separately. We measured levels of POMC primary transcript, processing intermediate and fully spliced mRNA in the nuclear fractions and POMC mRNA in cytoplasmic fractions. Compared to 0600 h, levels of POMC primary transcript decreased significantly during the afternoons of both proestrus and estrus (P < 0.05). Levels of nuclear processing intermediate RNA and cytoplasmic mRNA followed the same trend but the afternoon declines did not reach statistical significance. We conclude from these data that the afternoon decline in POMC gene expression is not unique to the day of proestrus and we speculate that an afternoon decline in beta-endorphinergic neuronal activity may instead be a component of the daily signal for the LH surge.

Animals↗

PubMed1993

Assessment of gene expression and peptide secretion from individual cells.

We have developed an assay that allows one to monitor gene expression in and peptide secretion from individual cells. By combining the reverse hemolytic plaque with in situ hybridization, investigators can quantitate simultaneously the level of gene expression and the level of secretion of a peptide. The method can be used in any system in which an appropriate antibody for the reverse hemolytic plaque assay and probes complementary to the mRNA of interest are available. It can be used to monitor the level of mRNA and secretion of the peptide product, or expression of one gene and the secretion of another peptide. In this paper we will describe the major steps of the method. We have used the pituitary lactotroph as a model to demonstrate the power of this technique. However, we believe that this method may be an important approach to answer many questions regarding the cellular and molecular mechanisms that regulate the coupling of peptide secretion and gene expression at the single cell level.

Animals↗

PubMed1992

Simultaneous monitoring of pituitary hormone secretion and gene expression within individual cells.

We have recently developed a method to simultaneously quantitate the level of gene expression and the level of secretion of a peptide from individual cells. Our approach has been to combine the reverse hemolytic plaque assay sequentially with in situ hybridization. We present data to show how we have used the pituitary lactotroph as a model to demonstrate the power of this technique. However, we are particularly excited about the potential application of this strategy to approach a broad spectrum of questions regarding the cellular and molecular mechanisms that regulate the coupling of peptide secretion and gene expression at the single cell level. The method can be used in any system in which an appropriate antibody for the reverse hemolytic plaque assay and probes complementary to the mRNA of interest are available.

Animals↗

PubMed1992

Aging abolishes the estradiol-induced suppression and diurnal rhythm of proopiomelanocortin gene expression in the arcuate nucleus.

The diurnal rhythms of many physiological functions are disrupted during aging. Underlying these disruptions are age-related alterations in the activity of neurotransmitters and/or their receptors. Estradiol has a significant influence on the pattern of the diurnal rhythms in neurotransmitter function, and responsiveness to estradiol changes with age. We assessed POMC mRNA levels in the arcuate nucleus of young, middle-aged, and old female rats to determine whether aging alters the diurnal rhythm of POMC gene expression in ovariectomized rats and/or changes the responsiveness to estradiol. In addition, we measured serum LH, PRL, and corticosterone levels to evaluate any age-associated interactions between these hormones and POMC mRNA levels. In young animals, estradiol treatment induced a diurnal rhythm and suppressed mean levels of POMC mRNA. In the middle-aged and old rats, the ability of estradiol to suppress POMC mRNA levels and to allow the expression of a diurnal rhythm of POMC mRNA was abolished. Although age-associated changes occurred in serum concentrations of LH, PRL, and corticosterone, they did not correlate with the changes in POMC gene expression. Therefore, our data demonstrate that age-related changes in hypothalamic POMC gene expression do not determine the changes in pituitary hormone secretion. Instead, they suggest that fundamental changes in diurnal function or in the biological clock underlie and differentially regulate the age-related changes in POMC gene expression and LH, PRL, and corticosterone secretion.

Aging↗