Circadian and circannual study of the hypophyseal-gonadal axis in healthy young males

Circadian and circannual variations of Testosterone, FSH and LH secretions, other than Oral Body Temperature (OBT) have been studied in four healthy males. OBT showed a constant circadian rhythm with an acrophase located in the afternoon. Plasma Testosterone exhibited both a circadian (acrophase = hr 09,28) and a circannual rhythm (acrophase = 22 february); plasma FSH also showed a circannual rhythm (acrophase = 13 february). By mean chronogram +/- SEM we documented the highest LH levels in December and the lowest in February. These observations would suggest the hypothesis that the winter could be the period in which the hypophysis-gonadal axis in young males exhibits its maximal activity as previously documented for other hormones.     

Comparison of the circadian rhythm in cell proliferation in corneal epithelium of male rats studied under normal and hypobaric (hypoxic) conditions

Groups of 20-45-day-old rats maintained on a light (0600-1800)/dark (1800-0600) regimen with food and water available ad libitum were studied for the effect of hypoxic hypoxia on the circadian rhythm of corneal epithelial mitosis and thymidine incorporation. In experiments conducted during the months of September and November, hypoxic hypoxia was accomplished by the exposure of rats to a simulated altitude of 7500 m in one series of experiments, or to a gaseous mixture of 8% oxygen and 92% nitrogen at sea level atmospheric pressure (760 mmHg) in another series of experiments. Controls were included as well. Statistically significant (P less than 0.05) circadian rhythmicity in the corneal mitotic index was substantiated in the control animals with mesor (M) = 12.4%, amplitude (A) = 9.6% and acrophase (phi) of 0911. In the hypoxic hypoxia situation, the mesor and amplitude were depressed to 8.6 and 5.9%, respectively. In control groups, thymidine incorporation was circadian rhythmic with M = 38.5 and A = 11.3 cpm/microns DNA and acrophase of 2255. In the hypoxic hypoxia situation, the mesor was similar to the controls; whereas the amplitude was suppressed to 6.1% and acrophase was phase advanced by about 7 hr. Changes in the circadian rhythm of corneal mitosis and in thymidine incorporation under hypoxic hypoxia can be explained by programmed-in-time energy requirements during the corneal cell regeneration cycle.     

Regulation of the 24h body temperature rhythm of women in luteal phase: role of gonadal steroids and prostaglandins

An investigation into whether the rise in the 24h body temperature rhythm observed in the luteal menstrual phase is antagonized by the administration of prostaglandin synthesis inhibitors has been made. Intravaginal body temperature was monitored continuously for 24h, once in the follicular and twice in the luteal phase. In the luteal phase, women were studied both without and with the simultaneous administration of a prostaglandin synthesis inhibitor (lysine acetylsalicylate; 1.8 g every 6 h orally). The progesterone/estradiol ratio (measured at 17:00h each day) was related to mesor (r = 0.825; P < 0.001), acrophase (r = 0.682; P < 0.02), and amplitude (r = -0.731; P < 0.001) of the 24h body temperature rhythm. Luteal phase elevation of the progesterone/estradiol ratio was associated with a 0.32 +/- 0.07 degrees C increase in mesor (P < 0.01), a 0.11 +/- 0.02 degrees C decrease in amplitude (P < 0.001), and a 34.8 +/- 11.6 min delay in acrophase (P < 0.03) of the 24h body temperature rhythm. Prostaglandin synthesis inhibitors did not counteract these modifications. The present data shows that the modifications of the circadian parameters of the 24h body temperature rhythm observed during the luteal phase of the menstrual cycle are strictly related to modifications of the progesterone/estradiol ratio, and presumably independent of prostaglandin synthesis.     

Intragastric pH and Pharmacokinetics of Intravenous Ranitidine During Sinusoidal and Constant-Rate Infusions

Six patients with healed duodenal ulcer completed two treatment periods with continuous i.v. infusion ranitidine. A 25-mg i.v. bolus was followed by a constant infusion at 6.25 mg/h or a sinusoidal infusion with infusion rates ranging from 3.125 to 9.375 mg/h. The sinusoidal infusion rate was designed to match the previously observed circadian changes in basal acid secretion. The peak infusion rate occurred at 19:30 h. A pharmacokinetic method was designed to predict the resultant plasma concentrations of ranitidine. Intragastric pH and plasma ranitidine concentration data were fit to a cosine function to evaluate circadian and ultradian rhythms. Plasma concentrations during the sinusoidal infusion exhibited a circadian rhythm according to model predictions. Cosinor analyses of the mean ranitidine plasma concentration data showed a mesor concentration of 237 ng/mL and amplitude of 76 ng/mL (coefficient of determination [CD] = 0.98). The acrophase in plasma concentration occurred at 2223 h, a delay of approximately 2.9 hours from the peak in the infusion rate. The constant-rate infusion resulted in a mean plasma concentration of 222 ± 32 ng/mL. The 24-h mean intragastric pH values for the sinusoidal and constant regimens were 5.4 and 5.1, respectively (p = 0.170). The intragastric pH during the constant-rate infusion exhibited a significant circadian rhythm (CD = 0.52). The minimum pH (bathy-phase) occurred at 2031 h. No circadian rhythm was present during the sinusoidal-rate infusion (CD = 0.08). At the approximate time of the peak basal acid secretion, between 21:00 hours and midnight, the mean pH for the sinusoidal infusion was 5.77 versus 4.5 for the constant-rate infusion (p = 0.112). Sinusoidal infusions or alternate methods of increased doses at the times of peak acid output may improve around-the-clock control of intragastric pH.     

Seasonal variations of LH, prolactin, androstenedione, testosterone and testicular FSH binding in the male blue fox (Alopex lagopus)

The seasonal changes in testicular weight in the blue fox were associated with considerable variations in plasma concentrations of LH, prolactin, androstenedione and testosterone and in FSH-binding capacity of the testis. An increase in LH secretion and a 5-fold increase in FSH-binding capacity were observed during December and January, as testis weight increased rapidly. LH levels fell during March when testicular weight was maximal. Plasma androgen concentrations reached their peak values in the second half of March (androstenedione: 0.9 +/- 0.1 ng/ml: testosterone: 3.6 +/- 0.6 ng/ml). A small temporary increase in LH was seen in May and June after the breeding season as testicular weight declined rapidly before levels returned to the basal state (0.5-7 ng/ml) that lasted until December. There were clear seasonal variations in the androgenic response of the testis to LH challenge. Plasma prolactin concentrations (2-3 ng/ml) were basal from August until the end of March when levels rose steadily to reach peak values (up to 13 ng/ml) in May and June just before maximum daylength and temperature. The circannual variations in plasma prolactin after castration were indistinguishable from those in intact animals, but LH concentrations were higher than normal for at least 1 year after castration.     

Effect of octreotide on 24-hour growth hormone and prolactin secretory patterns in acromegalics.

Four adult patients with active acromegaly underwent studies of their 24-hour secretory pattern of hGH and Prl prior to and at the end of 3 months of treatment with the octreotide (somatostatin analog SMS 201-995) 100 micrograms s.c. every 8 h. Blood was withdrawn at 30-min intervals with the aid of a constant withdrawal pump. The best fit cosinor method was used to define the following rhythm parameters: mesor, amplitude, acrophase and periodicity. Prior to treatment, hGH secretion was increased in all patients. The mean 24-hour ranged from 9-47 ng/ml with amplitude 5.2-23 and observed maximal pulse 41-95 ng/ml. Computed rhythms were circadian in 3 patients and ultradian in 1; in 2 patients the acrophases were shifted to daytime. hPrl secretion was altered in 3 of the patients. Two had elevated mean 24-hour of 17.7 and 22.2 ng/ml, while computed rhythms showed semicircadian periodicity in 1 of them and circadian periodicity with a shift of acrophase to daytime in the other. The third patient who had normal hPrl levels, showed ultradian 8-hour periodicity. At the end of treatment there was a marked reduction in hGH secretion in 1 patient and a lesser reduction in the other 3. The rhythm was influenced by the masking effect of the drug, to yield an 8-hour period with acrophases related to injection clock time having equal amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diurnal variations and temporal coupling of bioactive and immunoactive luteinizing hormone, prolactin, testosterone and 17-beta-estradiol in adult men.

Diurnal variations and temporal coupling in the circulating levels of immunoactive and bioactive luteinizing hormone (LH) and prolactin (PRL), testosterone (T) and 17-beta-estradiol (E2) in plasma of 6 healthy men (mean age 33 years) were studied. Each hormonal profile was analyzed for circadian amplitude, acrophase and nadir. Acrophases for immunoactive LH and T were coincident and ranged between clock hours 1 and 5. Acrophase for bioactive LH ranged between 9 and 12 h and was coincident with nadir for T. Acrophase for E2 ranged between 15 and 18 h and was coincident with nadir for immunoactive LH (15-17 h). Acrophase for bioactive PRL and immunoactive PRL ranged between 20-23 and 23-4 h, respectively. The circadian amplitude for T showed a negative correlation coefficient with circadian amplitude of bioactive LH (alpha = -0.86) and positive correlation coefficient with circadian amplitude of immunoactive LH (alpha = 0.94). It is inferred that immunoactive LH may be a sensor of T concentration while bioactive LH may be actually involved in the feedback regulation of T secretion. It is suggested that PRL may have a key role in the regulation of LH secretion.     

Circadian rhythm changes in core temperature over the menstrual cycle: method for noninvasive monitoring

The purpose of this study was to determine whether core temperature (T(c)) telemetry could be used in ambulatory women to track changes in the circadian T(c) rhythm during different phases of the menstrual cycle and, more specifically, to detect impending ovulation. T(c) was measured in four women who ingested a series of disposable temperature sensors. Data were collected each minute for 2-7 days and analyzed in 36-h segments by automated cosinor analysis to determine the mesor (mean temperature), amplitude, period, acrophase (time of peak temperature), and predicted circadian minimum core temperature (T(c-min)) for each cycle. The T(c) mesor was higher (P < or = 0.001) in the luteal (L) phase (37.39 +/-0.13 degrees C) and lower in the preovulatory (P) phase (36.91 +/-0.11 degrees C) compared with the follicular (F) phase (37.08 +/-0.13 degrees C). The predicted T(c-min) was also greater in L (37.06 +/- 0.14 degrees C) than in menses (M; 36.69 +/- 0.13 degrees C), F (36. 6 +/- 0.16 degrees C), and P (36.38 +/- 0.08 degrees C) (P < or = 0. 0001). During P, the predicted T(c-min) was significantly decreased compared with M and F (P < or = 0.0001). The amplitude of the T(c) rhythm was significantly reduced in L compared with all other phases (P < or = 0.005). Neither the period nor acrophase was affected by menstrual cycle phase in ambulatory subjects. The use of an ingestible temperature sensor in conjunction with fast and accurate cosinor analysis provides a noninvasive method to mark menstrual phases, including the critical preovulatory period.     

Effect of a melatonin implant on the circadian variation of plasma prolactin and rectal temperature in newborn sheep.

Plasma prolactin and rectal temperature show a circadian rhythm in newborn sheep raised under continuous light. Melatonin lowers the concentration of plasma prolactin but it is not known if it affects its circadian rhythm. To detect whether melatonin acts on the circadian system we studied the effect of a subcutaneous melatonin implant in the circadian rhythms of prolactin and rectal temperature in newborn lambs raised under continuous light. We placed catheters in the pedal artery and vein in 9 newborn lambs (2-5 days of age). A subcutaneous melatonin implant was placed in 4 of the lambs at 9-12 days of age. Blood samples and rectal temperature measurements were obtained hourly for a period of 24 h, 11-15 days after the implant, at 20-27 days of age. To avoid interferences of heparin in our melatonin assay, serum melatonin concentration was measured before and during the implant in three additional newborns. Prolactin and melatonin were measured by RIA. Melatonin concentrations were 52.8 +/- 45.9 pg/ml (day) and 315.5 +/- 77.0 pg/ml (night) before treatment (SEM, P less than 0.001), and increased to 594.1 +/- 54.5 pg/ml after placing the implant (there was no difference in melatonin concentration between day and night during the time that the implant was in place). Melatonin had no effect on rectal temperature or its rhythm, but decreased basal plasma prolactin concentration (control: 97.5 +/- 11.3 ng/ml; treated: 25.1 +/- 2.4 ng/ml, P less than 0.001) and abolished the prolactin circadian rhythm, (Cosinor analysis): control: log prolactin (ng/ml) = 1.8 + 0.26 cos 15 (t - 11.16), p = 0.05; treated: log prolactin (ng/ml) = 1.2 + 0.14 cos 15 (t - 9.43), P = 0.36.     

Circadian Rhythms of Histatin 1, Histatin 3, Histatin 5, Statherin and Uric Acid in Whole Human Saliva Secretion

The circadian rhythms of histatins 1, 3, 5, of statherin and uric acid were investigated in whole human saliva. Histatins showed a rhythm approximately synchronous with salivary flow rate (acrophase around 5 pm), the higher amplitude pertaining to histatin 1 (about 50% of the mesor). Uric acid showed a large rhythm asynchronous with flow rate and histatin concentrations (4.4 ± 1.4 am). Statherin did not show a significant circadian rhythm on five of six volunteers. This finding confirms that the secretion route of statherin is different from that of histatins.     

Plasma concentrations of testosterone and LH in the male dog

Blood samples were withdrawn every 20 min from 3 conscious intact and 2 castrated mature males during non-consecutive periods of 12 h during the light and dark phases of the lighting schedule (intact dogs) and of 11 h during the light period (castrated dogs). In the intact dogs testosterone concentrations ranged from 0.4 to 6.0 ng/ml over the 24-h period. LH concentrations varied from 0.2 to 12.0 ng/ml. In all animals, LH peaks were clearly followed, after about 50 min, by corresponding testosterone peaks, but no diurnal rhythm could be established. LH concentrations in the castrated dogs were high (9.8 +/- 2.7 (s.e.m.) ng/ml), and still showed an episodic pattern in spite of the undetectable plasma testosterone levels.     

Ultradian, circadian and seasonal variations of plasma progesterone and LH concentrations during the luteal phase

The circadian variations in plasma progesterone (P) and LH concentrations were investigated in six women, aged 23-40 years. All were studied in the mid-luteal phase (7 +/- 2 days after LH mid-cycle surge). Experiments were conducted in autumn and in spring. Blood samples were obtained every 15 min for 24 hr. Plasma P and LH concentrations were measured by RIA. Each subject's time-series was analysed using three methods; visual inspection (chronogram), spectral analysis to estimate component periods of rhythms (tau) and cosinor analysis to quantify the rhythms parameters. Marked temporal variations in plasma P concentration were observed in each subject. The maximal variations over a 24-hr period, ranged between 13-58.5 mmol/l. Differences related to sampling time were statistically validated by ANOVA (p less than 0.00001). Significant harmonic periods were detected by spectral analysis but differed among subjects. In all subjects but one, a circadian rhythm was detected. The acrophase location was similar (about 0700 hr) in the four subjects studied in autumn, but ranged from 1940 to 0320 hr in those studied in spring. An ultradian rhythm with tau = 8 hr was also validated in six time-series with similar acrophases (about 0200, 1000, and 1800 hr). Cosinor analysis of pooled data revealed that the 24-hr, 12-hr, and 8-hr rhythms were statistically significant (p = 0.001) in autumn. algebraic sum of these three cosine functions yielded a circadian waveform with peak-times occurring near 0300 and 1130 hr and a trough-time about 2200 hr. In spring, the circadian pattern appeared quite different, and peak-times were found near 0700 and 2000 hr, and trough-times near 0300 and 1500 hr. Furthermore, the 24-hr mean of P was higher in autumn (28.9 +/- 0.4 nmol/l) than in spring (17.2 +/- 0.4 nmol/l), p from ANOVA less than 0.00001. The evidence for a similar circadian LH pattern is not as strong. Seasonal, circadian and ultradian rhythms characterize the physiologic time structure of plasma P concentration in mid-luteal phase.     

Effects of gonadotropin-releasing hormone pulse-frequency modulation on luteinizing hormone, follicle-stimulating hormone and testosterone secretion in hypothalamo/pituitary-disconnected rams

The effects of changes in pulse frequency of exogenously infused gonadotropin-releasing hormone (GnRH) were investigated in 6 adult surgically hypothalamo/pituitary-disconnected (HPD) gonadal-intact rams. Ten-minute sampling in 16 normal animals prior to HPD showed endogenous luteinizing hormone (LH) pulses occurring every 2.3 h with a mean pulse amplitude of 1.11 +/- 0.06 (SEM) ng/ml. Mean testosterone and follicle-stimulating hormone (FSH) concentrations were 3.0 +/- 0.14 ng/ml and 0.85 +/- 0.10 ng/ml, respectively. Before HPD, increasing single doses of GnRH (50-500 ng) elicited a dose-dependent rise of LH, 50 ng producing a response of similar amplitude to those of spontaneous LH pulses. The effects of varying the pulse frequency of a 100-ng GnRH dose weekly was investigated in 6 HPD animals; the pulse intervals explored were those at 1, 2, and 4 h. The pulsatile GnRH treatment was commenced 2-6 days after HPD when plasma testosterone concentrations were in the castrate range (less than 0.5 ng/ml) in all animals. Pulsatile LH and testosterone secretion was reestablished in all animals in the first 7 days by 2-h GnRH pulses, but the maximal pulse amplitudes of both hormones were only 50 and 62%, respectively, of endogenous pulses in the pre-HPD state. The plasma FSH pattern was nonpulsatile and FSH concentrations gradually increased in the first 7 days, although not to the pre-HPD range. Increasing GnRH pulse frequency from 2- to 1-hour immediately increased the LH baseline and pulse amplitude. As testosterone concentrations increased, the LH responses declined in a reciprocal fashion between Days 2 and 7. FSH concentration decreased gradually over the 7 days at the 1-h pulse frequency. Slowing the GnRH pulse to a 4-h frequency produced a progressive fall in testosterone concentrations, even though LH baselines were unchanged and LH pulse amplitudes increased transiently. FSH concentrations were unaltered during the 4-h regime. These results show that 1) the pulsatile pattern of LH and testosterone secretion in HPD rams can be reestablished by exogenous GnRH, 2) the magnitude of LH, FSH, and testosterone secretion were not fully restored to pre-HPD levels by the GnRH dose of 100 ng per pulse, and 3) changes in GnRH pulse frequency alone can influence both gonadotropin and testosterone secretion in the HPD model.     

Fluctuation in responsiveness of LH and lack of responsiveness of FSH to prolonged infusion of morphine and naloxone in the ewe

In ewes in the mid-luteal phase, LH pulse frequency (P less than 0.01) and amplitude (P less than 0.05) increased during a 24 h infusion of naloxone (0.5 mg/kg/h) compared to a 24 h infusion of vehicle (mean +/- s.e.m.; 0.25 +/- 0.03 vs 0.14 +/- 0.01 pulses/h and 0.84 +/- 0.08 vs 0.55 +/- 0.08 ng/ml serum, respectively). The increase in pulse amplitude was immediate, but was less (P less than 0.05) during the second 12 h, compared to the first 12 h, of naloxone infusion (0.52 +/- 0.14 vs 0.98 +/- 0.08 ng/ml serum). Oestradiol concentrations were higher (P less than 0.01) during naloxone than during control infusion (5.63 +/- 0.26 vs 4.13 +/- 0.15 pg/ml serum). In ovariectomized ewes in the breeding season, LH pulse frequency was lower (P less than 0.01) during a 24 h infusion of morphine (0.5 mg/kg/h) than during a 24 h infusion of vehicle (mean +/- s.e.m.; 1.17 +/- 0.08 vs 1.71 +/- 0.06 pulses/h). We conclude that long-term infusion of naloxone results in a sustained increase in LH pulse frequency but only a transient elevation in pulse amplitude. No effects on FSH secretion were noted. LH secretion was sensitive to morphine in the absence of ovarian steroids, suggesting that ovarian steroids are not required for the presence of functional opioid receptors capable of modulating LH release.     

Plasma Corticosterone, Motor Activity and Metabolic Circadian Patterns in Streptozotocin-Induced Diabetic Rats

Experiments were conducted in male rats to study the effects of streptozotocin-induced diabetes on circadian rhythms of (a) plasma corticosterone concentrations; (b) motor activity; and (c) metabolic patterns. Animals were entrained to LD cycles of 12: 12 hr and fed ad libitum.

A daily rhythm of plasma corticosterone concentrations was found in controls animals with peak levels at 2400 hr and low values during the remaining hours. This rhythm was statistically confirmed by the cosinor method and had an amplitude of 3.37μg/100 ml and the acrophase at 100 hr. A loss of the normal circadian variation was observed in diabetic animals, with a nadir at the onset of light period and high values throughout the remaining hours; cosinor analysis of these data showed no circadian rhythm, delete and a higher mean level than controls.

As expected, normal rats presented most of their motor activity during the dark period with 80+ of total daily activity; the cosinor method demonstrated a circadian rhythm with an amplitude of 60+ of the mean level and the acrophase at 0852 hr. Both diabetic and control rats showed a similar activity during the light phase, but diabetic animals had less activity than controls during the night and their percentage of total daily activity was similar in both phases of the LD cycle (50+ for each one). With the cosinor method we were able to show the persistence of a circadian rhythm in the motor activity of diabetic rats, but with a mesor and amplitude lower than in controls (amplitude rested at 60+ of the mean level) and its acrophase advanced to 0148 hr.

The metabolic activity pattern of diabetic rats also changed: whereas controls showed a greater metabolic activity during the night (70+ food; 82+ water; 54+ urine; 67+ faeces), diabetics did not show differences between both phases of the LD cycle. Water ingested and urine excreted by the diabetic group were higher than normal during light and dark periods; food consumed and faeces excreted were higher than controls only in the light phase.

These data suggest that alterations in circadian rhythms of plasma corticosterone and motor activity are consecutive to the loss of the feeding circadian pattern, due to polyphagia and polydipsia showed by these animals, which need to extend intakes during the light and dark phases.     

Circadian temperature rhythm of laboratory swine

The circadian temperature rhythm (CTR) profile holds promise for monitoring the domestic pig's responses to stress and illness. In the present study we quantified the CTR profile of nine growing-finishing swine using a time-series, small-group design. Temperature was monitored using a probe implanted in the ear for 5 1/2 to 9 1/2 consecutive days while the unrestrained pigs were housed singly in pens. The dominant period of the temperature data was estimated with the autocorrelation function and then used in standard cosinor analysis to compute the amplitude (half of the distance between the highest and lowest value within the period), mesor (rhythm-adjusted mean), and acrophase (timing of the cosine maximum). To examine the effect of procedural stress on CTR, we compared data from the first 3 days with those from subsequent days. Eight of the nine (89%) pigs had CTR with a mean (+/- standard error) period of 23.6 (0.5) h, amplitude of 0.18 (0.02) degrees C, mesor of 38.7 (0.24) degrees C, and acrophase at 19:44 h. Mean mesor and acrophase were not different, but amplitude was lower (P = 0.03) during the first 3 days after instrumentation than during subsequent days. We conclude that: 1) laboratory-housed, unrestrained, growing-finishing swine have CTR; 2) our ear-based instrumentation protocol imposes acute stress as reflected in attenuated CTR amplitude during the first 3 days after instrumentation; and 3) CTR adaptation to stress appears to occur over time.     

The aging Leydig cell: 1. Testosterone and adenosine 3',5'-monophosphate responses to gonadotropin stimulation in rats

Plasma testosterone levels before and after a single injection of hCG were significantly lower in 24-month old rats than 60--90 day old animals (p less than 0.001). Even with repeated hCG administration for three weeks, plasma testosterone levels of old rats could not be restored to levels present in unstimulated young rats. In response to in vitro LH and 8-bromo-cyclic AMP stimulation, purified young Leydig cells produced significantly higher amounts of testosterone than Leydig cells from old rats. Maximal testosterone formation of the young Leydig cells in response to LH was 42.0 +/- 6.88 ng/10(6) cells, while cells from old rats produced only 16.8 +/- 3.69 ng/10(6) cells (p less than 0.01). However, the dose of LH at which one half maximal response (ED50) occurred was 0.1 mIU/ml for young Leydig cells and 0.05 mIU/ml for old Leydig cells. Basal and 1.0 mIU LH-stimulated cyclic AMP formation were comparable in both groups, but cyclic AMP formation in response to 10 mIU of LH was significantly less in the old rats (p less than 0.05). Present results demonstrate impaired steroidogenic capacity of old rats both in vivo and in vitro. Decreased testosterone response in old rats most likely is the consequence of understimulation of Leydig cells by gonadotropin; however, there appear to be additional intrinsic defects in old Leydig cells.     

Total and free testosterone in plasma of hypo- and agonadal men.

Plasma total testosterone (T), apparently free T and testosterone binding globulin (TeBG) capacity determined in 14 normal men aged 30-40 years were 461 +/- 100 ng/100 ml, 9.4 +/- 3.0 ng/100 ml and 5.7 +/- 1.9 X 10(-8) M, respectively, whereas in 16 hypogonadal men the corresponding values were 38.6 +/- 27.2 ng/100 ml, 0.47 +/- 0.41 ng/100 ml and 10.4 +/- 3.4 X 10(-8) M showing the TeBG capacity significantly higher (p less than 0.001) in hypogonadal than in normal men. Treatment of 5 hypogonadal subjects with 250 mg testosterone enanthate plus 50 mg testosterone propionate decreased (p less than 0.001) the TeBG level from 14.7 +/- 2.5 X 10(-8YM to 8.3 +/- 1.4 X 10(-8) M on day 8 after a single injection. According to this difference in TeBG, the free T fraction in plasma rose from 0.94% to 1.9% of the total T concentration. These results suggest that alteration of total plasma T affected the TeBG capacity. Decreased T levels raised and increased T concentrations suppressed TeBG, but with a delayed response to the changed T concentrations. The initial mean values in 12 patients with prostatic cancer aged 60-74 years were 397 +/- 165 ng/100 ml, 4.05 +/- 1.8 ng/100 ml and 11.9 +/- 3.3 X 10(-8) M, respectively. The TeBG capacity in these patients was significantly higher and the free T concentration significantly lower (p less than 0.001) than those of the younger normal males. After treatment with 12 g diethylstilbestrol diphosphate and orchidectomy, the TeBG increased to 33.3 +/- 13.1 X 10(-8) M and the plasma free T concentration decreased to the minimal value of 0.053 +/- 0.04 ng/100 ml.     

Postnatal development of TRH and TSH rhythms in the rat

We previously observed that under a 12-hour light/12-hour dark schedule (lights off at 19.00 h), adult male Sprague-Dawley rats showed a circadian rhythm for serum thyroid-stimulating hormone (TSH) with a zenith near midday. In the present work, the ontogenesis of serum TSH rhythm was determined as well as pituitary TSH variations. In addition, hypothalamic and blood TRH were measured in these rats aged 15, 25, 40 and 70 days when sacrificed. As from the first age studied (15 days), a hypothalamic thyrotropin-releasing hormone (TRH) circadian rhythm was present. The mesor and the amplitude of this hypothalamic TRH rhythm increased while the rats were growing up, in contrast with the decrease observed for these parameters as far as blood TRH circadian rhythm is concerned. The time of the acrophase moved from 17.32 h in the 15-day-old rats to 13.57 h in the 70-day-old rats, being constantly in phase opposition with the blood TRH acrophase. The low amplitude pituitary TSH circadian rhythm detected in the young rat disappeared in the adult while, in contrast, the serum TSH rhythm became consistent to reach the well-characterized circadian midday peak in the 70-day-old rats.     

The retino-hypothalamic tract is involved in prolactin regulation in fetal sheep.

To investigate the role of the retino-hypothalamic tract on fetal prolactin regulation, we examined the effect of ocular enucleation on fetal plasma prolactin. Eleven fetuses of Suffolk ewes were chronically catheterized during fall, and six of them were subjected to bilateral ocular enucleation. All ewes were kept at 12h:12h light:dark cycle (lights on at 0800 and off at 2000). The experiments were performed 5-9 days after surgery (GA control fetuses 125 +/- 1.5, optical enucleation 121.3 +/- 1.5 days). Blood samples were taken from fetuses hourly around the clock, and plasma prolactin and cortisol were measured by radioimmunoassay (RIA). Luteinizing hormone (LH) and Growth hormone (GH) were measured in pooled plasma samples from control and enucleated fetuses by RIA. Average plasma prolactin was 5-fold lower in enucleated than in control fetuses (9.6 +/- 0.5 and 54.2 +/- 3.3 ng/ml, SEM; P < 0.005). Both control and enucleated fetuses presented circadian rhythm of prolactin with acrophase between 1400 and 1830 h. An enucleated fetus was tested for response of prolactin to TRH. Prolactin increased as described in the literature. There was no change in plasma concentration of cortisol, LH or GH after ocular enucleation. Our data indicate that the optical pathway participates in prolactin regulation in the fetal sheep.