Individualized cosinor assessment of circadian hormonal variation in third trimester human pregnancy

Two clinically healthy pregnant women were studied in a single 24-h span during the third trimester. Blood drawn every 20 min was assayed for cortisol (F), dehydroepiandrosterone sulfate (DHEA-S), estriol (E3), and prolactin (PRL). Blood drawn hourly was assayed for progesterone (P), human placental lactogen (HPL) and 15alpha-hydroxyestriol (E4). Breast temperature (BT) was continuously monitored. Single cosinor analysis demonstrated statistically significant circadian rhythms for plasma concentrations of F, DHEA-S, and BT for both subjects, and of E3 for one subject. Statistically significant circadian rhythms in plasma concentrations of P, HPL, E4 or PRL could not be demonstrated in our third trimester subjects. However, analysis of data from subjects sampled at earlier gestational ages revealed highly significant PRL circadian rhythms. These results suggest that plasma concentrations of PRL show a progressive decrease in circadian amplitude despite a progressive increase in mesor with advancing gestational age. Frequent sampling and cosinor data analysis permit identification of circadian rhythms in BT. The use of BT as a potential marker for rhythms in plasma concentration of certain hormones awaits further scrutiny. The demonstration of several circadian endocrine rhythms in individual subjects in the third trimester of human pregnancy facilitates the usefulness of such marker rhythms.     

Twenty-four-hour secretory patterns of cortisol,progesterone and estradiol in heifers during the follicular and luteal phases of the ovarian cycle

Daily variations of plasma cortisol, progesterone and estradiol concentrations were measured by radioimmunoassay in six different normally cycling heifers during estrus (day 1 of the cycle) and diestrus (days 12–15 of the cycle). Each animal was fitted with an indwelling jugular catheter, and blood was withdrawn at 30-min intervals over a 24-h period. Statistical evaluation of the hormonal profiles using time series analysis revealed that all three steroids are secreted episodically with secretory episodes varying in number, magnitude and timing among different heifers. After dividing the 24-h into three 8-h time periods (I, 09.00–17.00 h; II. 17.00–01.00h; III, 01.00–09.00 h) a prominent circadian rhythm was found for cortisol during estrus and diestrus. Diurnal periodicity similar to that of cortisol was noticed for plasma progesterone during estrus but not diestrus when a functional corpus luteum was present. Estradiol secretion during the follicular and luteal phase of the estrous cycle was characterized by intermittent sustained elevations lasting about 9–15 h and marked by a graded rise and fall of hormone levels unrelated to photoperiod.From our results obtained in cycling heifers we conclude the following: (1) Plasma cortisol exhibits a distinct circadian rhythm during estrus and diestrus which is highly correlated with the light–dark cycle. (2) Plasma progesterone during estrus demonstrates a diurnal pattern which is absent in diestrous heifers bearing a corpus luteum. (3) Plasma estradiol lacks circadian rhythmicity but shows a distinct pattern different from that of progesterone, indicating that both steroids are secreted independently and not controlled by a circadian pacemaker.     

Circadian and circannual rhythms of hormonal variables in elderly men and women

A group of fourteen men (73 ± 5 yr of age), and eighteen women (77 ± 7 yr of age) institutionalized at the Berceni Clinical Hospital, Bucharest, Romania, were studied over a 24-hr span once during each season (winter, spring, summer and fall). All subjects followed a diurnal activity pattern with rest at night and ate three meals per day with breakfast at about 0830, lunch at about 1300 and dinner at about 1830. The meals were similar, although not identical for all subjects during all seasons. On each day of sampling blood was collected at 4-hr intervals over a 24-hr span. Seventeen hormonal variables were determined by radioimmunoassay. Statistically significant circadian rhythms were detected and quantitated by population mean cosinor analysis in pooled data from all four seasons in both sexes for ACTH, aldosterone, Cortisol, C-peptide, dehydroepiandrosterone-sulfate (DHEA-S), immunoreactive insulin, prolactin, 17-OH progesterone, testosterone, total T₄ and TSH. In women, estradiol and progesterone also were determined and showed a circadian rhythm during all seasons. Total T, and FSH showed circadian rhythm detection by cosinor analysis in the men only; LH showed no consistent circadian rhythm as group phenomenon in men or women.

A circannual rhythm was detected using the circadian means of each subject at each season as input for the population mean cosinor in the women for ACTH, C-peptide, DHEA-S, FSH, LH, progesterone, 17-OH progesterone and TSH. In the men, a circannual rhythm was detected for ACTH, FSH, insulin, LH, testosterone and T₃. There were phase differences between men and women in ACTH, FSH and LH. In those functions in which both the circadian and circannual rhythms were statistically significant, a comparison of the amplitudes showed in the women a higher circannual rather than circadian amplitude for DHEA-S. In 17-OH progesterone, TSH and C-peptide, the circadian amplitude in women was larger. In men, the circannual amplitude of T₃ was larger than the circadian amplitude and in insulin the circadian amplitude was larger than the circannual amplitude. There was no statistically significant difference between the circadian and circannual amplitudes in the women in ACTH and progesterone and in the men in ACTH and testosterone.     

Circadian and Circannual Rhythms of Hormonal Variables in Elderly Men and Women

A group of fourteen men (73 ± 5 yr of age), and eighteen women (77 ± 7 yr of age) institutionalized at the Berceni Clinical Hospital, Bucharest, Romania, were studied over a 24-hr span once during each season (winter, spring, summer and fall). All subjects followed a diurnal activity pattern with rest at night and ate three meals per day with breakfast at about 0830, lunch at about 1300 and dinner at about 1830. The meals were similar, although not identical for all subjects during all seasons. On each day of sampling blood was collected at 4-hr intervals over a 24-hr span. Seventeen hormonal variables were determined by radioimmunoassay. Statistically significant circadian rhythms were detected and quantitated by population mean cosinor analysis in pooled data from all four seasons in both sexes for ACTH, aldosterone, Cortisol, C-peptide, dehydroepiandrosterone-sulfate (DHEA-S), immunoreactive insulin, prolactin, 17-OH progesterone, testosterone, total T₄ and TSH. In women, estradiol and progesterone also were determined and showed a circadian rhythm during all seasons. Total T, and FSH showed circadian rhythm detection by cosinor analysis in the men only; LH showed no consistent circadian rhythm as group phenomenon in men or women.

A circannual rhythm was detected using the circadian means of each subject at each season as input for the population mean cosinor in the women for ACTH, C-peptide, DHEA-S, FSH, LH, progesterone, 17-OH progesterone and TSH. In the men, a circannual rhythm was detected for ACTH, FSH, insulin, LH, testosterone and T₃. There were phase differences between men and women in ACTH, FSH and LH. In those functions in which both the circadian and circannual rhythms were statistically significant, a comparison of the amplitudes showed in the women a higher circannual rather than circadian amplitude for DHEA-S. In 17-OH progesterone, TSH and C-peptide, the circadian amplitude in women was larger. In men, the circannual amplitude of T₃ was larger than the circadian amplitude and in insulin the circadian amplitude was larger than the circannual amplitude. There was no statistically significant difference between the circadian and circannual amplitudes in the women in ACTH and progesterone and in the men in ACTH and testosterone.     

Rhythms in the ovulatory cycle. 3rd: Cortisol and dehydroepiandrosterone sulphate (DHEA-S)

The circadian profiles of cortisol and dehydroepiandrosterone sulphate (DHEA-S) were analyzed in a homogeneous group of 15 young normally cycling women, at 4 times of the menstrual cycle: early follicular (EF), late follicular (LF), early luteal (EL) and late luteal (LL) stages. The circatrigintan variations of the same hormones were also evaluated. Population-mean cosinor analysis allowed the demonstration of a highly significant circadian periodicity for both variables in any of the 4 stages of the menstrual cycle; on the other hand, the same computation failed to demonstrate a significant circatrigintan periodicity. In each of the stages considered, the circadian acrophase of DHEA-S was delayed in comparison to that of cortisol, being located in the early afternoon hours. The demonstration of a clear-cut circadian oscillation in serum DHEA-S prompts studies on possible chrono-abnormalities of the steroid production in women with hyperandrogenic diseases.     

Effect of bromocriptine on the control of plasma aldosterone diurnal variation in normal supine man.

In order to investigate the role of prolactin in the control of the circadian rhythm of plasma aldosterone (PA), plasma renin activity (PRA), cortisol (PC), aldosterone and prolactin (PRL) levels were determined in samples at 4-hour intervals from 5 normal supine men over a period of 24 h under basal conditions and subsequently over a period of 24 h during suppression of prolactin release by bromocriptine (CB-154). After suppression of prolactin, statistically signific1nt circadian rhythms in PC and PA have been detected with a moderate decrease of PA concentration, while the PC level remained unalterated. PRA rhythmicity persisted with a significant shift of acrophase and remarkable reduction of plasma levels. Moreover, during CB administration a significant correlation was obtained between PA and PC, while no correlation was detected between PA and PRA. These data are consistent with the following concepts: (a) the prolactin does not play a significant role in the regulation of circadian rhythm and concentration of plasma aldosterone in normal supine men, and (b) bromocriptine induces a remarkable reduction of PRA and a variable decrease in plasma aldosterone, but it does not influence the secretion of cortisol in normal subjects.     

Age-Related Circadian Rhythm of DHEAS Plasma Levels in Male Subjects

The aging influences the endocrine temporal structure, including DHEAS which can be considered as a biomarker of aging, since its levels gradually decrease in older subjects. The aim of this work was to observe the circadian rhythms of DHEAS, prolactin, cortisol and body temperature, in healthy elderly male subjects (73.7 ± 2.5 years) compared with healthy young subjects (27.2 ± 6.6 years). The results documented that in our subjects no significant age-related differences in prolactin levels existed. In elderly subjects cortisol levels were weakly enhanced in comparison with young subjects. DHEAS showed a preserved circadian rhythm, but markedly lower rhythm adjusted mean (74.38 ± 10.29 versus 273.63 ± 26.39) (p < 0.001) and decreased amplitude of oscillation (p < 0.001), when expressed as absolute value, in elderly subjects when compared with young subjects. In elderly subjects the DHEAS circadian rhythm modifications could represent an impairment of of the endocrine temporal structure.     

Hypoxic alterations of cortisol circadian rhythm in man after simulation of a long duration flight

Fatigue is often reported after long duration flights. Mild hypobaric hypoxia caused by pressurisation may be involved in this effect through disruption of circadian rhythms, independently of the number of time zones crossed. In this controlled crossover study, we assessed the effects of two levels of hypoxia equivalent to 8000 and 12,000 ft on the circadian rhythm of plasma cortisol, a marker of the circadian time structure. Sixteen healthy young male volunteers (23-39 years) were exposed in a hypobaric chamber for 8 h (08:00-16:00 h) to 8000 ft, followed 4 weeks later to 12,000 ft. Plasma cortisol was assayed during two 24-h cycles (control and hypoxic exposure) every 2h in all subjects. We found a significant change in the pattern of cortisol secretion during both hypoxic exposures, with an initial fall in cortisol followed by a transient rebound, whereas the phase and the 24-h mean level remained unchanged. The change in cortisol pattern followed the alterations in autonomic balance assessed by heart rate variability (HRV) spectral analysis. The normalised high frequencies and the low-to-high frequencies ratio showed a significant shift toward sympathetic dominance with some differences in time course for both altitudes studied. HRV analysis improved the interpretation of cortisol 24-h profiles. Our data, which strongly suggest that prolonged mild hypoxia alters the expression of cortisol circadian rhythm, should be taken into account to interpret secretory rhythm changes after transmeridian flights.     

Development of Salivary Cortisol Circadian Rhythm and Reference Intervals in Full-Term Infants

BackgroundCortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life.Methods130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist.ResultsA significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life.ConclusionsCortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants.     

Gender specific correlations of adrenal gland size and body fat distribution: a whole body MRI study.

OBJECTIVE: The aim of this study was to investigate the gender specific correlations of stress related tissues [adrenal gland volume (AV), visceral fat] and alimentary dependent fat compartments with cortisol concentrations in healthy male and female subjects. METHODS: Fourteen men and 13 women were examined. Fat compartments [whole body fat, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SCAT)] were determined using whole body MRI. Adrenal gland volume was assessed by a 3D MR data set. The salivary cortisol was determined at 9 AM and 4 PM. RESULTS: Men had significantly more visceral fat and less subcutaneous fat than women. Adrenal gland size correlated significantly with the visceral and subcutaneous fat in women (r=0.7, p=0.008), but not in men (r=0.2, p=0.4). There was a negative correlation between the decrease of cortisol between 9 AM and 4 PM with VAT (r=-0.451, p=0.027) in the whole group. DISCUSSION: The high correlation between the adrenal gland volume and VAT in women underlines the link between hypothalamic-pituitary-adrenal (HPA) axis, stress, and circadian cortisol rhythm, respectively, and an increased abdominal fat volume. The lack of correlation between visceral fat and adrenal volume in men points to an additional influence of sex hormones.     

A method to evaluate dynamics and periodicity of hormone secretion

Spontaneous hormone secretory dynamics include tonic and pulsatile components and a number of periodic processes. Circadian variations are usually found for melatonin, TSH and GH, with peak secretions at night, and in cortisol secretion, which peaks in the morning. Free thyroxine (FT4) and insulin-like growth factor (IGF)1 levels do not always change with circadian rhythmicity or show only minor fluctuations. Fractional variations explore the dynamics of secretion related to time intervals, and the rate of change in serum levels represents a signal for the receptorial system and the target organ. We evaluated time-related variations and change dynamics for melatonin, cortisol, TSH, FT4, GH and IGF1 levels in blood samples obtained every 4 h for 24 h from eleven healthy males, ages 35-53 years (mean ? SE 43.6 ± 1.7). Nyctohemeral (i.e., day-night) patterns of hormone secretion levels and the fractional rate of variation between consecutive 4-hourly time-qualified hormone serum levels (calculated as percent change from time 1 to time 2) were evaluated for circadian periodicity using a 24 and 12-h cosine model. A circadian rhythm was validated for serum level changes in cortisol with peaks of the 24-h cosine model at 07:48 h, and melatonin, TSH and GH, with phases at 01:35 h, 23:32 h, and 00:00 h, respectively. A weak, but significant, 12-h periodicity was found for FT4 serum levels, with minor peaks in the morning (10:00 h) and evening (22:00 h), and for IGF1, with minor peaks in the morning (07:40 h) and evening (19:40 h). Circadian rhythmicity was found in the 4-hourly fractional variations with phases of increase or surge at 02:00 h for cortisol, 22:29 h for melatonin, 05:14 h for FT4, and 21:19 h for GH. A significant 12-h periodicity was found for the 4-hourly fractional variations of TSH with two peaks in the morning (decrease or drop at 04:42 h) and afternoon (surge at 16:28 h), whereas IGF1 fractional variation changes did not show a significant rhythmic pattern. In conclusion, the calculation of the time-qualified fractional rate of variation allows evaluation of the dynamics of secretion and the specification of the timepoint(s) of maximal change of secretion, not only for hormones whose secretion is characterized by a circadian pattern of variation, but also for hormones that show no circadian or only weak ultradian (12 h) variations (i.e., FT4).     

Rhythms in the ovulatory cycle. 2nd: LH, FSH, estradiol and progesterone

The circadian profiles of LH, FSH, estradiol and progesterone were compared in a homogeneous group of 15 young normally cycling women, at 4 well characterized times of the menstrual cycle: early follicular (EF), late follicular (LF), early luteal (EL) and late luteal (LL) stages. The circatrigintan profiles of the same hormones were also evaluated. Population-mean cosinor analysis failed to demonstrate a circadian periodicity of LH in any of the 4 stages of the menstrual cycle; a circadian rhythm for FSH was present only in the 2 luteal phases (EL, LL); the same type of rhythmicity was present for estradiol only in the late luteal stage; on the contrary, a highly significant circadian rhythm of progesterone was present in each of the 4 menstrual stages considered (EF, LF, EL and LL). Population-mean cosinor analysis showed a highly significant circatrigintan periodicity of LH and FSH with the acrophases respectively between -109 degrees and -181 degrees and between -74 degrees and -125 degrees. Circatrigintan rhythmicity was also present for estradiol (acrophases between -161 degrees and -245 degrees) and progesterone (acrophases between -246 degrees and -296 degrees).     

Cefodizime administration in healthy subjects: studies of natural killer cells, urinary hormones and electrolytes

Two studies are here discussed: the first one on changes of the natural killer cell activity of PBM cells exposed in vitro to CDZ and the second one on urinary electrolytes, cortisol, aldosterone and DHEA-S circadian rhythms, evaluated in healthy subjects who received a single dose (2 g i.v.) of cefodizime (CDZ). The effect of CDZ in health includes a reduction of the circadian amplitude of natural killer cell activity. With the methods used, no difference was found between placebo and CDZ, as far as circadian rhythms of urinary electrolytes, cortisol, aldosterone and DHEA-S are concerned.     

Possible linkage between the ability to change the period (tau) of the prolactin and cortisol rhythms in women and breast cancer risk

The 24 h profiles of plasma hormone concentrations are rhythmic. The circadian period (τ) changes in development, with seasons, and in women with different stages of the menstrual cycle. It is known that the rhythms of prolactin and cortisol are sensitive to environmental time cues, such as changes in day length and phase; however, the importance of these changes is not yet understood. This study investigates whether there is a relation between the ability of a subject to respond to external cues that are associated with seasonal changes causing alteration of the rhythm's periods in cortisol and prolactin and the epidemiologically determined susceptibility to breast cancer. It is shown that the rhythmic output pattern of prolactin and cortisol in vivo is generated by more than one oscillator and structured by more than one rhythmic component. Each cohort of American women, classified on an epidemiologic basis as high risk (HR) or low risk (LR) to develop breast cancer, expresses different rhythmic output patterns of both variables, suggesting that the genetic background as defined by the risk state is related to differences in the circadian time structure, including the ability of the subject to change the rhythm's τ. The LR cohort exhibited a statistically significant change between seasons in the rhythm's τ of both the prolactin and cortisol patterns. In contrast, the HR cohort showed no change in the rhythm's τ between seasons for prolactin and cortisol patterns. These results show that in human beings, the presence of a circannual rhythm in the circadian time structure or the ability to adapt the circadian rhythmic pattern of these variables to external cues, such as seasons, is related to the partly genetically determined risk state to develop breast cancer and may be of importance for human health.     

Oscillations in the Activities of Enzymes of Nitrate Reduction and Ammonia Assimilation in Glycine max and Zea mays

The activities of glutamate dehydrogenase (GDH), glutamine synthetase (GS), and nitrate reductase (NR) and the levels of soluble protein and NO^-₃ were assayed in soybean (Glycine max [L.] Merr.) leaves over a 48-h period with the initial 24 h under a light-dark cycle (LD 16:8) followed by 24 h of continuous light (LL). Plants had been entrained for 30 days under the LD regime. Maize (Zea mays) leaves (10 days old) under a LD 15:9 cycle were assayed only for NR and nitrite reductase (NiR). Data were subjected to frequency analysis by the least squares method to determine probabilities for cosine function periods (τ's) between 10 and 30 h. NR activities for both soybean and Zea leaves had 24 h τ's with P values < 0.05 indicating circadian periodicity. GDH in soybeans had a 24-h rhythm under LD conditions which lengthened under LL conditions. The 24-h rhythm of GDH displayed maximal activity toward the end of the dark period of the LD cycle whereas the highest activity of NR was early in the light period. Total soluble protein displayed a rhythm with a best fitting τ of greater than 24 h under both LD and LL. GDH, GS, NR, NO₃, and soluble protein in soybeans and NiR in Zea, all displayed that were ultradian (10–18 h), indicating that a τ of about one half a circadian periodicity may be a common characteristic of the enzymes of primary nitrogen metabolism in higher plants. These data also demonstrate that although both NR and GDH are circadian in their activity, the 24-h rhythm may be greatly influenced by ultradian oscillations in activity.     

Influence of administration of pyridoxine on circadian rhythm of plasma ACTH, cortisol prolactin and somatotropin in normal subjects

The influence of vitamin B6 in a dosage of 300 mg X 2 in 24 hrs, on circadian rhythm of plasmatic ACTH, cortisol, prolactin and somatotropin have been studied in 10 normal women. After vitamin B6 24 hrs pattern of ACTH and cortisol is unchanged; prolactin levels are slightly lower, in a statistically unsignificant proportion the night peak of growth hormone is higher in a statistically significant proportion (p. 0.05). The effect of vitamin B6 is likely to me mediated by dopaminergic receptors at hypothalamic level as previous studies by other Authors appear to prove.     

Effects of sulpiride on levels of FSH, LH and steroid hormones

In order to study the effects of prolactin upon the gonadotrophins and steroid hormones, hyperprolactinaemia was induced by the administration of sulpiride. 12 men between the ages of 18 and 20 were given 3 capsules of 50 mg of sulpiride daily for a period of 15 days, and the following parameters being measured before and after the treatment: (prolactine, FSH, LH, testosterone, estradiol, ACTH and DHEA-S) by RIA, (cortisol) by fluorimetry and (etiocholanone, androsterone, pregnandiol, pregnantriol, pregnantriolone, 11-keto etiocholanone and 11-OH androsterone) by gas chromatography. Our results show that on termination of the treatment there was a significant rise in the prolactin and DHEA-S serum levels and a drop in the FSH serum levels but not of LH. In addition there was a marked increase in all the androgen levels studied, (etiocholanone, androsterone and 11-keto etiocholanone) with the exception of testosterone.     

The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects

Exogenous melatonin (0.5-10 mg) has been shown to entrain the free-running circadian rhythms of some blind subjects. The aim of this study was to assess further the entraining effects of a daily dose of 0.5 mg melatonin on the cortisol rhythm and its acute effects on subjective sleep in blind subjects with free-running 6-sulphatoxymelatonin (aMT6s) rhythms (circadian period [tau] 24.23-24.95 h). Ten subjects (9 males) were studied, aged 32 to 65 years, with no conscious light perception (NPL). In a placebo-controlled, single-blind design, subjects received 0.5 mg melatonin or placebo p.o. daily at 2100 h (treatment duration 26-81 days depending on individuals' circadian period). Subjective sleep was assessed from daily sleep and nap diaries. Urinary cortisol and aMT6s were assessed for 24 to 48 h weekly and measured by radioimmunoassay. Seven subjects exhibited an entrained or shortened cortisol period during melatonin treatment. Of these, 4 subjects entrained with a period indistinguishable from 24 h, 2 subjects continued to free run for up to 25 days during melatonin treatment before their cortisol rhythm became entrained, and 1 subject appeared to exhibit a shortened cortisol period throughout melatonin treatment. The subjects who entrained within 7 days did so when melatonin treatment commenced in the phase advance portion of the melatonin PRC (CT6-18). When melatonin treatment ceased, cortisol and aMT6s rhythms free ran at a similar period to before treatment. Three subjects failed to entrain with initial melatonin treatment commencing in the phase delay portion of the PRC. During melatonin treatment, there was a significant increase in nighttime sleep duration and a reduction in the number and duration of daytime naps. The positive effect of melatonin on sleep may be partly due to its acute soporific properties. The findings demonstrate that a daily dose of 0.5 mg melatonin is effective at entraining the free-running circadian systems in most of the blind subjects studied, and that circadian time (CT) of administration of melatonin may be important in determining whether a subject entrains to melatonin treatment. Optimal treatment with melatonin for this non-24-h sleep disorder should correct the underlying circadian disorder (to entrain the sleep-wake cycle) in addition to improving sleep acutely.     

Ovine prolactin potentiates the action of adrenocorticotropic hormone on the secretion of dehydroepiandrosterone sulfate and dehydroepiandrosterone from cultured bovine adrenal cells

To determine the direct effect of prolactin on adrenal androgen secretion, the daily secretions of dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione and cortisol were determined in monolayer culture of bovine adrenal cells in the presence or absence of adrenocorticotropic hormone (ACTH) and/or prolactin. In the absence of ACTH ovine prolactin alone had no effect on steroid secretion during seven-day culture. Ovine prolactin, when administered in combination with ACTH, significantly potentiated the stimulatory effect of ACTH on DHEA-S and DHEA but not androstenedione secretion on the seventh day in culture. On the first day in culture prolactin showed no synergistic effect with ACTH on DHEA and DHEA-S secretion, although ACTH significantly increased DHEA and cortisol secretion. DHEA-S secretion increased as a function of prolactin concentration in the presence of ACTH. These results indicated that long-term treatment by ovine prolactin with ACTH caused the increase in adrenal androgen secretion from bovine adrenal cells. The site of action of prolactin was suggested to be the partial inhibition of adrenal 3 beta-hydroxysteroid dehydrogenase by the result of increases in DHEA-S and DHEA but not androstenedione secretion.     

Effect of thyroidectomy on rhythmic gonadotropin release.

Nonstress blood samples were obtained from intact and thyroidectomized (TE) male rats at 3-hr intervals over a 24-hr period via rapid decapitation. The animals were thyroidectomized when 40 days old and used 6 weeks later. Intact animals showed periodicity in serum LH (P less than 0.01) and prolactin (P less than 0.01). Both gonadotropins began increasing after 8 PM and peak levels occurred at 11 PM. In contrast, 24-hr periodicity was not observed in serum FSH. Corticosterone levels in these same serum samples showed the expected circadian periodicity. After TE, the 24-hr pattern in all gonadotropins was altered significantly. Serum LH increased (P less than 0.01) and circadian periodicity appeared to be absent. FSH and prolactin levels were increased and decreased, respectively (P less than 0.01), with serum prolactin showing a 9-hr phase shift. Prolactin began increasing at 2 AM and reached a peak at 8 AM. Corticosterone in TE animals showed a 24-hr rhythm similar to that of intact rats. These findings confirm our previous observations that nonstress serum LH and prolactin levels fluctuate with a 24-hr periodicity and suggest that the level of, and the phase angle betweeen, these rhythms is markedly influenced by pituitary-thyroid activity.