Altered Brain Structure in Infants with Turner Syndrome.

Turner syndrome (TS) is a genetic disorder affecting approximately 1:2000 live-born females. It results from partial or complete X monosomy and is associated with a range of clinical issues including a unique cognitive profile and increased risk for certain behavioral problems. Structural neuroimaging studies in adolescents, adults, and older children with TS have revealed altered neuroanatomy but are unable to identify when in development differences arise. In addition, older children and adults have often been exposed to years of growth hormone and/or exogenous estrogen therapy with potential implications for neurodevelopment. The study presented here is the first to test whether brain structure is altered in infants with TS. Twenty-six infants with TS received high-resolution structural MRI scans of the brain at 1 year of age and were compared to 47 typically developing female and 39 typically developing male infants. Results indicate that the typical neuroanatomical profile seen in older individuals with TS, characterized by decreased gray matter volumes in premotor, somatosensory, and parietal-occipital cortex, is already present at 1 year of age, suggesting a stable phenotype with origins in the prenatal or early postnatal period.

Neoplasia and granulomas surrounding microchip transponders in Damaraland mole rats (Cryptomys damarensis).

Damaraland mole rats (Cryptomys damarensis) are among the longest-living rodents, with a maximum longevity of approximately 16 years. As one of the few mammals termed eusocial, these animals have been used in behavioral, genetic, metabolic, and physiologic research at the University of Connecticut since 1997. For individual identification at 3 to 4 months of age, mole rats were subcutaneously implanted with microchip transponders (11 mm in length) in the dorsal cervical region. In 2007, 2 of the 90 implanted adults, 10-year-old and 9-year-old females, developed subcutaneous masses at the site of the implant. Histopathological and immunohistochemical examinations revealed amelanotic melanoma and fibrosarcoma, respectively, with metastasis of the amelanotic melanoma. In 2008, a total of 3 adult males were castrated as part of a sex behavior study; 3 months later, all 3 castrated males developed subcutaneous masses around their implants, whereas none of the noncastrated males had masses. After an additional 9 months, these masses were found to be granulomas. To the authors' knowledge, this is the first report of neoplasia in this species. Both the tumors and the granulomas surrounded the microchip transponder.

Melatonin induction of gonadal quiescence in pinealectomized Syrian hamsters.

Pinealectomized Syrian hamsters were injected thrice daily with 25 micrograms of melatonin per injection. The injections were administered at 3-hour intervals either during the day or during the night of a photoperiodic cycle of 14 hours of light and 10 hours of darkness. After 6 weeks of treatment with melatonin during the night, both pinealectomized and intact hamsters had reduced testis weight, and pinealectomized hamsters showed decreased levels of serum gonadotropins. Injection of melatonin during the day for 7 weeks either once (75 micrograms) a day or thrice (25 micrograms per injection) daily caused a reduction in testis weight in pinealectomized hamsters. Both pinealectomized and intact females injected with melatonin thrice daily during the day became anovulatory by week 7 of treatment. These results are similar to those observed when hamsters are exposed to a short photoperiod, suggesting that melatonin may be acting as a hormone in mediating the effects of photoperiod on the reproductive system of the Syrian hamster.

Avian pancreatic polypeptide phase shifts hamster circadian rhythms when microinjected into the suprachiasmatic region.

The suprachiasmatic nucleus has been identified tentatively as a circadian pacemaker. To examine the functional role of peptides found within suprachiasmatic neurons, avian pancreatic polypeptide and vasopressin were microinjected into the suprachiasmatic region. Avian pancreatic polypeptide, but not vasopressin, shifted the phase of the wheelrunning rhythm as a function of the time of its injection within the circadian cycle. Avian pancreatic polypeptide or a similar peptide may be one component of the neurochemical processes underlying entrainment to the light-dark cycle.

Vasopressin injected into the hypothalamus triggers a stereotypic behavior in golden hamsters.

Microinjection of arginine vasopressin into the medial preoptic area of the hypothalamus of male and female golden hamsters triggered a complex, stereotypic behavior--flank marking--a type of scent marking used in olfactory communication. The flank marking was not elicited by saline, oxytocin, neurotensin, or angiotensin II. Vasopressin was ineffective when injected into other areas of the hypothalamus or into the lateral cerebroventricle.

Distribution of oxytocin in the brain of a eusocial rodent.

Naked mole-rats are highly social rodents that live in large colonies characterized by a rigid social and reproductive hierarchy. Only one female, the queen, breeds. Most colony members are non-reproductive subordinates that work cooperatively to rear the young and maintain an underground burrow system. Little is known about the neurobiological basis of the complex sociality exhibited by this species. The neuropeptide oxytocin (Oxt) modulates social bonding and other social behaviors in many vertebrates. Here we examined the distribution of Oxt immunoreactivity in the brains of male and female naked mole-rats. As in other species, the majority of Oxt-immunoreactive (Oxt-ir) cells were found in the paraventricular and supraoptic nuclei, with additional labeled cells scattered throughout the preoptic and anterior hypothalamic areas. Oxt-ir fibers were found traveling toward and through the median eminence, as well as in the tenia tecta, septum, and nucleus of the diagonal band of Broca. A moderate network of fibers covered the bed nucleus of the stria terminalis and preoptic area, and a particularly dense fiber innervation of the nucleus accumbens and substantia innominata was observed. In the brainstem, Oxt-ir fibers were found in the periaqueductal gray, locus coeruleus, parabrachial nucleus, nucleus of the solitary tract, and nucleus ambiguus. The high levels of Oxt immunoreactivity in the nucleus accumbens and preoptic area are intriguing, given the link in other rodents between Oxt signaling in these regions and maternal behavior. Although only the queen gives birth or nurses pups in a naked mole-rat colony, most individuals actively participate in pup care.

Serum silicon levels are elevated in women with silicone gel implants.

The metabolic fate of silicone gel leaked into the body from an implant is unknown. In this study, serum from 72 women with silicone gel breast implants and 55 control women was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon. Samples were processed using materials free of silicon. The mean silicon level in controls was 0.13 +/- 0.07 mg/l (range 0.06-0.35 mg/l), while in implant patients, the mean was significantly higher at 0.28 +/- 0.22 mg/l (range 0.06-0.87 mg/l) (P < 0.01, Student's t-test with correction for unequal variances). Using the mean of the control group + 2 SD as a cutoff for normal range (0.27 mg/l), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw or the number of years with implants and silicon levels. The results suggest that elevations of serum silicon are seen in many women with silicone gel breast implants. The kinetics of this elevation and the actual chemical species of the measured silicon remain to be determined.

Pleiotropic expression of heterologous cytokine/receptor genes in HTLV-1 associated diseases: candidate TRS for chimeric gene therapy.

DNA motifs that encode for specific transcriptional regulatory sequences (TRS) when engineered adjacent to the structural protein coding domain of a suicide enzyme can provide cell-lineage specific protein expression. The disparate up-regulation of several genes in adult T-cell leukemia (ATL) versus HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), seropositive carriers (SPC) and uninfected normals may reflect events at the molecular level related to leukemogenesis or to processes maintaining the heme-oncologic phenotype. Further, the genetic transduction of cytokine and receptor genes uniquely associated with ATL may provide targets for the development of leukemia-specific gene therapies aimed at exploiting differences in the production of certain growth factors and growth factor receptors. Comparisons of the transcriptional and translational levels of interleukin-2 receptor alpha chain (IL-2R alpha), transforming growth factor-beta 1 (TGF-beta 1) and intracellular adhesion molecule-1 (ICAM-1) in ATL, HAM/TSP, and SPC and in several control populations revealed selectively up-regulated expression in ATL. We evaluated the feasibility of using lymphoid-specific TRS to activate herpes simplex virus thymidine kinase (HSVtk) to achieve selective cytotoxicity in leukemias expressing terminal deoxynucleotidyl transferase (TdT). Selective and efficient leukemic cell killing was produced and suggests that similar chimeric gene constructs containing TRS elements for IL-2R alpha, TGF-beta 1, or ICAM-1 may prove useful in designing gene therapies to treat ATL.

Mammalian photoperiodic system: formal properties and neuroendocrine mechanisms of photoperiodic time measurement.

Photoperiodism is a process whereby organisms are able to use both absolute measures of day length and the direction of day length change as a basis for regulating seasonal changes in physiology and behavior. The use of day length cues allows organisms to essentially track time-of-year and to "anticipate" relatively predictable annual variations in important environmental parameters. Thus, adaptive types of seasonal biological changes can be molded through evolution to fit annual environmental cycles. Studies of the formal properties of photoperiodic mechanisms have revealed that most organisms use circadian oscillators to measure day length. Two types of paradigms, designated as the external and internal coincidence models, have been proposed to account for photoperiodic time measurement by a circadian mechanism. Both models postulate that the timing of light exposure, rather than the total amount of light, is critical to the organism's perception of day length. In mammals, a circadian oscillator(s) in the suprachiasmatic nucleus of the hypothalamus receives photic stimuli via the retinohypothalamic tract. The circadian system regulates the rhythmic secretion of the pineal hormone, melatonin. Melatonin is secreted at night, and the duration of secretion varies in inverse relation to day length; thus, photoperiod information is "encoded" in the melatonin signal. The melatonin signal is presumably "decoded" in melatonin target tissues that are involved in the regulation of a variety of seasonal responses. Variations in photoperiodic response are seen not only between species but also between breeding populations within a species and between individuals within single breeding populations. Sometimes these variations appear to be the result of differences in responsiveness to melatonin; in other cases, variations in photoperiod responsiveness may depend on differences in patterns of melatonin secretion related to circadian variation. Sites of action for melatonin in mammals are not yet well characterized, but potential targets of particular interest include the pars tuberalis of the pituitary gland and the suprachiasmatic nuclei. Both these sites exhibit uptake of radiolabeled melatonin in various species, and there is some evidence for direct action of melatonin at these sites. However, it appears that there are species differences with respect to the importance and specific functions of various melatonin target sites.

Evidence that the circadian system mediates photoperiodic nonresponsiveness in Siberian hamsters: the effect of running wheel access on photoperiodic responsiveness.

Juvenile male Siberian hamsters from a line of hamsters selected for nonresponsiveness to short photoperiod (PNRj) and animals from the general colony (UNS) were separated at weaning into two groups. Group 1 males were moved into short days (10 h light:14 h dark [10L:14D]) with free access to running wheels (RW). Group 2 animals were the male siblings of Group 1 hamsters; they were moved at the same time into the same room, but were housed in cages without access to RW. Group 2 hamsters only had access to RW for the final week of short-day exposure (Week 8). Animals were blood sampled at the time of sacrifice for analysis of serum prolactin (PRL) and follicle-stimulating hormone (FSH) concentrations. At sacrifice, paired testis weights were obtained and pelage color was scored. Animals from the UNS line showed the expected declines in testis weight, body weight, and serum concentrations of both PRL and FSH, regardless of the presence or absence of RW. These animals also exhibited a high proportion of individuals molting to winter-type pelage. By contrast, a marked difference was noted between siblings from the PNRj line depending on whether RW access was provided at the time of weaning. Animals with access to RW exhibited identical responses to those of the UNS responder animals, whereas PNRj animals without access to RW showed no adjustments to short days (i.e., testis regression, pelage molt, expansion of alpha). In a second experiment, PNRj and UNS males were placed in constant darkness (DD), with or without RW access. The results of this experiment indicated that PNRj animals respond to DD regardless of the presence or absence of RW. In DD, PNRj hamsters also exhibited significantly longer free-running period lengths (taus) than did UNS hamsters; all the PNRj hamsters had taus > 24 h, whereas none of the UNS hamsters had a tau > 24 h. These results indicate that PNRj hamsters retain the proper neural pathways for responding to short day lengths and establish a role for locomotor activity feedback in modulating the circadian system and, subsequently, photoperiodic responsiveness in PNRj hamsters.

Photoperiod nonresponsive Siberian hamsters: effect of age on the probability of nonresponsiveness.

Groups from three different breeding lines of Siberian hamsters (UNS = general colony animals, PNRa = selected for photoperiod nonresponsiveness as adults, PNRj = selected for photoperiod nonresponsiveness as juveniles) were exposed to short days at weaning and again as adults (Experiment 1) or only as adults (Experiment 2). The proportion of photoperiod nonresponsive individuals in each line was determined by measuring testis length after 6 weeks of exposure to short days (juveniles) or by paired testis weights after 12 weeks in short photoperiod (adults). Adults were blood sampled on the day of sacrifice (Experiment 1) or on Weeks 3, 4, 5, 6, 8, 10, and 12 (Experiment 2) for determination of serum prolactin (PRL) and follicle-stimulating hormone (FSH) concentrations. Nonresponsive individuals were present in all three lines of hamsters. Furthermore, all three lines of hamsters showed an increase in the proportion of nonresponders with age; some individuals are responsive to short days as juveniles, but become nonresponsive in adulthood. The two PNR lines exhibited a greater proportion of nonresponders at both ages compared to the UNS line, with the PNRj line exhibiting the greatest proportion of nonresponders at each age. During exposure to short days, nonresponders exhibited significantly higher serum PRL and FSH concentrations that did the UNS line; nonresponders also exhibited larger testis size, and fewer animals molted to winter-type pelage. The results indicate that (a) in all three lines, a significantly higher proportion of animals are nonresponsive to short photoperiod as adults than as juveniles; (b) selection for nonresponsiveness as juveniles can produce a line of hamsters that, as adults, are nearly all nonresponsive to short days; and (c) some individuals from each line are responsive to short photoperiod early in life, but become nonresponsive as adults.

Circadian regulation of pineal melatonin and reproduction in the Djungarian hamster.

Gonadal state, pineal melatonin rhythms, and locomotor activity rhythms were examined in juvenile male Djungarian hamsters exposed to non-24-hr light cycles ("T-cycles") or to full photoperiods. At the end of 1 month, hamsters exposed to a 1-hr pulse of light every 24.33 hr (T 24.33) exhibited small testes, whereas those receiving the same amount of light every 24.78 hr (T 24.78) displayed stimulated gonads, ten-fold larger in size. Accompanying the nonstimulatory effect of the T 24.33 cycle were nocturnal peaks in both pineal melatonin content and serum melatonin concentration which were longer by approximately 4 hr than those observed on the photostimulatory T 24.78 cycle. Exposure to an intermediate-length T-cycle (T 24.53) resulted in a mixed gonadal response and in pineal and serum melatonin peaks of intermediate duration. Wheel-running activity was entrained to the T-cycles such that light was present only near the beginning of the subjective night, its phase (relative to activity onset) differing only slightly among T-cycle groups. Hence the durational differences observed in the melatonin peaks were apparently not due to the acute suppressive or phase-advancing effects of morning light on melatonin biosynthesis, but were rather the result of differences in the endogenous control of pineal activity by the circadian pacemaker system. While no strong correlation was detected between gonadal state and the phase of locomotor activity onset relative to the light pulse, a significant correlation was observed between gonadal state and the duration of daily locomotor activity (alpha). These data were compared to similar measures obtained from hamsters exposed to long-versus short-day full photoperiods (LD 16:8 vs. LD 10:14). In summary, the results of this study indicate involvement of the circadian pacemaker system of Djungarian hamsters in the control of pineal melatonin synthesis and secretion, and in photoperiodic time measurement. Furthermore, these data strengthen the hypothesis that it is the duration of nocturnal pineal melatonin secretion that is the critical feature of this neuroendocrine gland's photoperiodic signal.

Genetic and environmental influences on short-day responsiveness in Siberian hamsters (Phodopus sungorus).

Siberian hamsters are photoperiodic rodents that typically exhibit several physiological changes when exposed to a short-day photoperiod. However, development of the winter phenotype in short days is largely conditional on prior photoperiod history: Hamsters that have been reared in an exceptionally long day length (18 L) do not usually exhibit the winter phenotype after transfer to short days, whereas animals reared under "moderately" long days (16 L) are more variable in responsiveness to subsequent short-day exposure, with 20% to 30% generally failing to exhibit winter-type responses. Hamsters reared exclusively in an "intermediate" day length (14 L) are almost uniformly responsive to short photoperiod. In the present study, the authors examine the influence of photoperiod history on short-day responsiveness in a breeding line of hamsters that has been subjected to artificial selection for resistance to the effects of short days. The results demonstrate that photoperiod history is an important determinant of short-day responsiveness in both random-bred (UNS) hamsters and animals artificially selected and bred for nonresponsiveness to short photoperiod (PNR). The PNR hamsters have a reduced requirement for long-day exposure to evoke a state of unresponsiveness to short days. The results are discussed in relation to possible significance for the origin of population and species differences in photoperiod responsiveness.

Effect of melatonin infusion duration and frequency on gonad, lipid, and body mass in pinealectomized male Siberian hamsters.

The goal of this study was to discriminate between two hypotheses regarding how the circadian rhythm of pineal melatonin (MEL) production transmits photoperiodic information: (1) A circadian rhythm of sensitivity to MEL regulates the hormone's effect; (2) the duration of the MEL signal, rather than its circadian timing, is the critical parameter of the MEL rhythm. The experiment examined the response of pinealectomized (PINX) male Siberian hamsters to 10-hr (short-day-type) versus 6-hr (long-day-type) duration MEL infusions (10 ng/infusion) in cycles with period lengths (T) of 18, 24, 36, and 48 hr. After cannula implantation, animals were moved from LD 16:8 to LD 10:14 (lights-on from 0500 to 1500 hr, EST), where the timed infusions began. Additional T 24 cycles included as controls employed 18-hr MEL, 18-hr saline (SAL), and 10-hr SAL infusions: Body weight and food intake were measured weekly. After 6 weeks, animals were killed; blood samples were taken for radioimmunoassay (RIA) of serum follicle-stimulating hormone (FSH) and prolactin (PRL); and terminal body, epididymal white adipose tissue (EPIWAT), and paired testis weights were recorded. Six-hour MEL infusions failed to induce short-day-type effects, regardless of the period (T) of the infusion cycle. In contrast, compared to SAL and 6-hr MEL infusions, 10-hr MEL resulted in decreases in body, EPIWAT, and testis weights in T 24, but not in T 36 or T 48. In T 18, testis, body, and EPIWAT mass were decreased, but not to the same extent as in T 24. Similarly, daily 18-hr MEL infusions (T24) were less effective as a short-day stimulus than were 10-hr MEL infusions. The effectiveness of 10-hr, but not 6-hr, MEL infusions in T 18 and T 24 is consistent with the duration hypothesis and argues against the circadian hypothesis. Neither hypothesis could have predicted that all infusion cycles of T greater than or equal to 36 hr, regardless of the infusion durations, would fail to elicit short-day-type responses. This outcome suggests a need for relatively frequent (T less than 36 hr) MEL stimulation in addition to the requirement for adequate duration of each MEL infusion.

Circadian patterns of locomotor activity and body temperature in blind mole-rats, Spalax ehrenbergi.

A wide variety of organisms exhibit circadian rhythms, regulated by internal clocks that are entrained primarily by the alternating cycle of light and darkness. There have been few studies of circadian rhythms in fossorial species that inhabit a microenvironment where day-night variations in most environmental parameters are minimized and where exposure to light occurs only infrequently. In this study, daily patterns of locomotor activity and body temperature (Tb) were examined in adult blind mole-rats (Spalax ehrenbergi). These fossorial rodents lack external eyes but possess rudimentary ocular structures that are embedded in the Harderian glands and covered by skin and fur. Most individual mole-rats exhibited circadian rhythms of locomotor activity, but some animals were arrhythmic. Individuals that did exhibit robust rhythms of locomotor activity also showed rhythms of Tb. In most cases, Tb was highest during the phase of intense locomotor activity. Locomotor activity rhythms could be entrained to light:dark cycles, and several mole-rats exhibited entrainment to non-24-h light cycles (T-cycles) with period lengths ranging from T = 23 h to T = 25 h. Some individuals also showed entrainment to daily cycles of ambient temperature. There was considerable interindividual variation in the daily patterns of locomotor activity among mole-rats in virtually all the conditions of environmental lighting and temperature employed in this study. Thus, whereas it appears likely that photic cues have a significant role in the entrainment of circadian rhythms in mole-rats, the amount of variability in rhythm patterns among individuals appears to be much greater than for most species that have been studied.

Influence of prenatal photoperiods on postnatal reproductive responses to daily infusions of melatonin in the Siberian hamster (Phodopus sungorus).

Prepubertal reproductive development in juvenile male Siberian hamsters can be strongly influenced by photoperiod information received during gestation. Information transmitted from the mother hamster to her fetuses appears to modify the photoperiodic mechanism of the developing hamsters so that they may respond differently to certain intermediate day lengths [i.e. 14 h of light and 10 h of darkness/day (14L)] experienced after birth depending on whether gestation occurred in longer or shorter day lengths. In adult and juvenile hamsters, the duration of the nocturnal elevation of pineal and serum melatonin (MEL) is an important component of the photoperiodic system coding for day length. In the present study, we investigated whether the photoperiod in effect during gestation could influence the responsiveness of developing male hamsters to daily MEL infusions of fixed durations administered after weaning. The results indicated that hamsters gestated under 16L or 10L did not differ from each other with respect to testicular growth in response to any of the fixed duration MEL infusions. Thus, target tissue responsiveness to fixed duration MEL infusions (over a range of 6-10 h) was the same regardless of the gestation photoperiod to which the animals had been exposed.

Gender differences in influence of prenatal photoperiods on postnatal pineal melatonin rhythms and serum prolactin and follicle-stimulating hormone in the Siberian hamster (Phodopus sungorus).

In Siberian hamsters, the rate of testicular maturation during juvenile life can be influenced by both the prenatal photoperiod and the day length experienced postnatally. In this report, potential postnatal photoperiodic mechanisms modified by prenatal photoperiod were investigated in this species. The study examined the effect of prenatal photoperiodic history on the postnatal pineal melatonin (MEL) rhythm and on postnatal secretion of FSH and PRL. In the first study, the pineal MEL content of hamsters, gestated in either 16 h of light and 8 h of darkness/day (16L) or 10L and raised postnatally in 14L, was monitored at various times of the day and night at 18 days of age. We found that prenatal photoperiod did influence the postnatal pineal MEL rhythm in 18-day-old males, but a similar effect was not evident in females. For males, the durations of the nocturnal elevation of pineal MEL were 8.5 and 7 h in 16L and 10L gestated hamsters, respectively. However, MEL rhythms were similar to each other in the corresponding groups of females (8.5- and 9-h durations of elevated pineal MEL in 16L and 10L prenatal photoperiod groups, respectively). In a subsequent study using the same photoperiod paradigm, FSH and PRL concentrations were examined in both genders at 3- to 10-day intervals between 18-62 days of age. The serum PRL (day 22) and FSH (days 18 and 22) concentrations in males were significantly affected by prenatal photoperiod. Specifically, circulating serum PRL (on day 22) and FSH (on days 18 and 22) concentrations were increased substantially in 10L gestated, compared to 16L gestated, males raised in 14L after birth. In contrast, serum FSH concentrations in female hamsters were not different between 16L and 10L gestated groups at these times. In another study using the same experimental design, the pattern of testicular development was explored in males. Hamsters that had experienced a 10L photoperiod prenatally and were raised in 14L exhibited rapid testicular growth from 27-52 days of age compared to hamsters that had experienced a 16L prenatal photoperiod and were reared in 14L. These results support the hypothesis that in juvenile male hamsters exposed to 14L postnatally, endogenous MEL production and serum FSH concentrations are influenced by photoperiodic information received during fetal life. In addition, these findings help to explain why males gestated in 10L and raised in 14L exhibit accelerated testicular development in the first 2 months of life compared to males gestated in 16L and transferred to 14L after birth.(ABSTRACT TRUNCATED AT 400 WORDS)

The relationship between the rat of testosterone infusion and gonadotropin secretion.

Prepubertal and young adult male rats were castrated and continuous intravenous infusions of testosterone were administered for 2-3 days. Blood samples were obtained at various intervals and serum concentrations of FSH and LH were determined. In 43-day-old males a dose of approximately 57 mug/day was required to suppress serum LH to levels observed in intact controls, and FSH was also suppressed at this dose. Within one day after termination of infusions serum LH and FSH concentration had returned to (or exceeded) the levels observed in castrates infused with vehicle only. This was true even after a very large dose of testosterone had been administered (918 mug/day). In 59-day-old males serum LH was suppressed somewhat by 40 mug testosterone/day and further by 200 mug/day. FSH did not appear to be suppressed as readily in these rats as compared to the younger animals. Further experiments in which castrated rats were injected with testosterone or testosterone propionate revealed marked differences in the magnitude and time course of the action of these compounds upon LH release. It is suggested that the rate of metabolism of these steroids is important in limiting their effects, especially when administered by single daily injections. Furthermore, it appears that "recovery" of the hypothalamic-pituitary system from exposure to high concentrations of testosterone is rapid following clearance of the steroid from the blood.

Serum gonadotropins and follicular development in the Syrian hamster.

Hamster serum gonadotropins were measured by RIA at 4 h intervals during the estrous cycle. On the afternoon of proestrus both LH and FSH exhibited a surge, but unlike the situation in the rat and mouse FSH returned to "baseline" with LH by early evening of proestrus. Shortly following this return FSH concentrations increased and reached a second peak by noon on estrus which was equal in magnitude and longer in duration than that occurring on proestrus. FSH fell to its lowest levels on diestrus 2 (D2) and early proestrus. Serum gonadotropins were measured by RIA 6 h following unilateral ovariectomy on D2. A slight elevation of LH resulted while FSH increased to a level equal in magnitude to that found during the proestrous surge. In intact females administration of a total of 45 mug FSH in 5 injections on D2 resulted in ovulation of twice the normal number of eggs. The t1/2 of this rat FSH in the male hamster was found to be 122 minutes. The low levels of FSH during the cycle between D2 and proestrus, the large increase in serum FSH following unilateral ovariectomy, and the "doubled" ovulation in intact hamsters following the administration of FSH on D2, suggest that the serum FSH concentration on D2 is critical in determining the number of follicles which will be available for the subsequent ovulation.

Ovarian control of prolactin secretion during late pregnancy in the rat.

The involvement of the ovaries during late pregnancy in the rat upon serum prolactin was investigated. Ovariectomy on day 17 or day 21 of pregnancy prevented the dramatic rise of prolactin found in sham-ovariectomized animals between days 21 and 23 of pregnancy. While animals ovariectomized on day 17 of pregnancy failed to carry viable fetuses beyond day 19 of pregnancy, rats ovariectomized on day 21 of pregnancy had viable pups in utero on day 23 of pregnancy. These data suggest that the rise in serum prolactin during late pregnancy is stimulated by ovarian factors.