Effects of electrochemical stimulation of the hypothalamus on serum prolactin and LH in rats

Summary Plasma levels of prolactin and LH were measured by radioimmunoassay following electrochemical stimulation of the medial preoptic area (MPO) or the arcuate nucleus (Arc.N.) in pentobarbital anesthetized proestrous rats. Differences in the secretion pattern of prolactin and LH were observed when stimulated by means of acutely or chronically implanted electrodes. Acute implantation and stimulation of the MPO resulted in no change in serum prolactin levels, whereas stimulation by means of chronically implanted electrodes evoked a marked increase in serum prolactin. The general observation was that electrostimulation in the acute experiments causes a less sharp but more prolonged prolactin and LH release from pituitary than stimulation through chronically implanted electrodes.Aided in part by NIH research grants CA 10771 and AM 4784.     

Impact of acute sleep restriction on cortisol and leptin levels in young women

Sleep restriction alters hormone patterns and appetite in men, but less is known about effects on women. We assessed effects of overnight sleep restriction on cortisol and leptin levels and on appetite in young women. Participants' baseline sleep duration and eating habits were monitored for a week before the study. Salivary cortisol and leptin were sampled from fifteen healthy women (aged 18-25) during two consecutive days: first after a 10 h overnight sleep opportunity (Baseline day) and then after a night including only 3 h sleep (Post sleep-restriction day). Participants also completed appetite questionnaires on both days. Sleep restriction significantly reduced morning cortisol levels (p = 0.02), elevated morning leptin levels (p = 0.04), elevated afternoon/evening cortisol area under the curve values (p = 0.008), and slowed the decline in cortisol concentration during the day (p = 0.04). Hunger and craving scores did not differ significantly between days. A single night of restricted sleep affected cortisol rhythms and morning leptin levels in young women.     

Effects of various oestrogens on circulating androgens and cortisol during replacement therapy in post-menopausal women

The influence of various oestrogens during unopposed replacement therapy on circulating androgens and cortisol was studied in 65 post-menopausal women. A dose dependent decrease in dehydroepian-drosterone sulphate (DHAS) was found. Ethinyloestradiol (0.05 mg daily) already gave a significant decrease after 1 mth of treatment. The decline following 17β-oestradiol (2 mg) and oestrone sulphate (2.5 mg) was less pronounced. Oestriol (6 mg daily) had no effect. Ethinyloestradiol also increased the levels of total cortisol and testosterone, probably because of serum protein induction, while 17β-oestradiol had no significant effect. Serum levels of androstendione remained unchanged during therapy.     

Effect of shift work on the night-time secretory patterns of melatonin,prolactin, cortisol and testosterone

Summary In a study of the internal desynchronization of circadian rhythms in 12 shift workers, 4 of them, aged 25–34 years, agreed to be sampled every 2 h during their night shift (0000 hours to 0800 hours). They were oil refinery operators with a fast rotating shift system (every 3–4 days). We found marked changes in the secretory profiles of melatonin, prolactin and testosterone. Melatonin had higher peak-values resulting in a four-times higher amplitude than in controls. With respect to prolactin and testosterone, peak and trough times were erratic and the serum concentrations were significantly decreased in shift workers. Serum cortisol presented a decreased rhythm amplitude together with higher concentrations at 0000 hours in shift workers. This study clearly shows that fast rotating shift-work modifies peak or trough values and rhythm amplitudes of melatonin, prolactin, testosterone and cortisol without any apparent phase shift of these hormones. Whether the large rhythm amplitude of melatonin may be considered as a marker of tolerance to shift work, as reported for body temperature and hand grip strength, since it would help the subjects to maintain their internal synchronization, needs further investigation.     

Production rates of androgens and oestrogens in post-menopausal women

The production rate (PR) values of Δ⁴-androstenedione (A), testosterone (T), oestrone (E_l) and oestradiol (E₂) have been determined in a large group of post-menopausal women following constant infusions of radiolabelled hormones and radioimmunoassay of endogenous steroid concentrations. The mean ± SE age was 64 ± 2 yr, ranging from 46 to 91 yr and the mean ± SE weight was 144 ± 4lb.

When the PR values were related to age by linear regression analysis no significant correlation could be found for PRA, PRT or PRE₁ and the age of the subjects. There was, however, a significant correlation between PRE₂ and age.

There was a significant correlation between the PR values for each of the four steroids and the weights and body surface areas of the subjects. In addition, PRA correlated directly with both PRT and PRE₁ in these subjects in which both PR values were measured.

The PR values for each steroid were significantly smaller in the post-menopausal women compared to the mean PR values of a large group of pre-menopausal women.

We conclude that age, per se, does not appear to influence the PR values for A, T and E₁ but does for E₂. The subject's weight, however, has a major influence for the PR values of all four steroids.     

Social influences on circulating levels of cortisol and prolactin in male talapoin monkeys

Three captive groups of adult talapoin monkeys (Miopithecus talapoin), each with four males and four or five ovariectomized, estrogen-treated females, were observed. Behavioral interactions were recorded and levels of cortisol and prolactin were measured. In each group, males formed a linear dominance order, determined by the direction of spontaneous aggression; highest male rank was associated with frequent socio-sexual interactions and lowest rank with infrequent socio-sexual behavior. The first study compared males' cortisol and prolactin titers when all males were either housed with estrogen-treated females, or singly caged. The two lowest-ranking males of each group had elevated cortisol levels when group-housed; prolactin levels did not reflect these changes. In the second study, males of one group interacted with females when only the lowest-ranking, or the highest-ranking, female was made attractive (i.e., received estradiol), while the other females were present, but not estradiol-treated. Across these conditions (1) frequencies of some socio-sexual and aggressive behaviors changed, (2) cortisol levels increased in all males, and (3) prolactin levels decreased in three of four males. Dissociation of changes in cortisol and prolactin titers suggests that these hormones may be differentially responsive to social modifications, not simply reflecting a single intervening variable, such as "stress."     

Serum concentrations of FSH, oestradiol, oestrone and androstenedione in normal and obese women

The normal ranges of the concentrations of follicle stimulating hormone (FSH), oestradiol (E2), oestrone (E1), and androstenedione (A) were established in 257 healthy women. The hormone levels of 84 normal post-menopausal women were compared with those from a group of 46 post-menopausal women with severe obesity (36.3 +/- 15.2 kg over the ideal weight). The increase of the FSH concentrations during the peri- and post-menopause occurs about 4 yr earlier in the obese than in the normal women. There is no significant difference, however, between the E2 levels of the normal and obese women. In the obese women, A (P less than 0.001) and E1 (P less than 0.05) levels are significantly lower than in the normal women. A weight reduction in the obese women had no influence on the concentrations of A and E2, whereas E1 levels tended to increase. FSH levels also increased significantly during weight reduction.     

Plasma and pituitary concentrations of LH,FSH and prolactin after injection of GnRH in aged female C57BL/6 mice

Plasma and pituitary concentrations of LH, FSH and prolactin (Prl) were compared by radioimmunoassay (RIA) in young mature (2–4 monthold) and aged (16–22 month-old) female C57BL/6 mice, following various experiments with IP injections of GnRH. Unanesthetized mice were bled by cardiac puncture either (1) at various time intervals following a single injection of 25 ng GnRH, (2) after several injections of 25 ng GnRH, or (3) after receiving excessively large doses of GnRH. From the RIA of plasma and pituitary concentrations of LH, it appeared that the pituitaries of aged mice were, in general, capable of responding to GnRH treatment, only to a lesser degree than that of the younger females. The exception was that the pituitaries of aged mice that were subjected to unusually high doses of GnRH continued to secrete higher levels of LH, whereas the response of the pituitaries in younger mice plateaued after receiving 25 ng GnRH. Plasma and pituitary concentrations of FSH and Prl remained fairly constant when aged GnRH-treated females were compared with aged controls. This was also true when FSH and Prl concentrations in the younger mice were compared with their controls, except for significantly higher plasma FSH and significantly lower pituitary FSH following several injections of GnRH. When the hormonal concentrations of the young and aged groups were compared in the various experiments, the older mice consistently exhibited higher levels of gonadotropin and lower levels of prolactin than those of the younger mice. In a separate experiment, in which a radioreceptor assay (RRA) was used to quantitate plasma LH in GnRH-treated mice, both age groups were found to have lower concentrations of LH (p<0.05) than those obtained by RIA from the same animals. The RRA to RIA ratio, however, was 0.84 for 2–4 month-old and 0.57 for 16–22 month-old mice. These studies suggest that the anterior pituitary of the aged mouse is less sensitive to GnRH stimulation.     

Plasma and pituitary concentrations of LH,FSH, and Prolactin in aging C57BL/6 mice at various times of the estrous cycle

—Plasma and pituitary concentrations of LH, FSH, and prolactin (Prl) were measured by RIA in 2–4, 7–8, 12–13 and 16–20 month-old female C57BL/6 mice during various stages of the estrous cycle. In general, gonadotropin concentrations tended to rise with increasing age and Prl concentrations tended to decline. Pronounced differences existed, however, between the four age groups around the time of the LH surge. LH secretion declined progressively with increasing age at 21.00 hr of proestrus. Aged mice, 16–20 months old, had significantly lower plasma concentrations of LH than did other age groups. It is not known whether age-related changes in the ovary, pituitary, or hypothalamus are largely responsible for differences in the secretion of LH, FSH and Prl in aging C57BL/6 mice.     

Poor sleep the night before an experimental stress task is associated with reduced cortisol reactivity in healthy women

Sleep disruption is a growing problem that may have serious health effects. As stress-induced increases in cortisol are thought to be a key adaptive process it is important to examine how this response is affected by sleep. The current study investigated the association of four sleep parameters (objective/subjectively measured sleep quality and quantity) and subsequent salivary cortisol reactivity (maximal change from baseline) to an experimental stressor in 53 healthy women. Objective actigraphy monitoring and self-report diaries were used to assess sleep. Results revealed that individuals with lower objective sleep quality (wake percentage during sleep) had a blunted response to the experimental stressor. No associations were found between cortisol reactivity and actigraphy-derived sleep quantity, or either of the self-reported sleep variables. Results are discussed with regard to the possible adverse health effects that may result from poor sleep quality and a blunted cortisol response to stress.     

Effect of oestriol on the oscillation of circulating gonadotrophins in post-menopausal women during sleep

The effect of oestriol on the rapid oscillation of circulating FSH and LH levels during sleep was investigated by administering oestriol (E₃: 2 mg/day) orally for 3 mth to 3 healthy post-menopausal women who experienced frequent hot flushes. Before treatment and at the end of the third mth of treatment, blood samples were drawn during the length of sleep, and serum FSH and LH levels were measured by radioimmunoassay. Fluctuations of serum FSH and LH levels were recorded and the pulses were defined as a 20% increase of hormone concentration over nadir. The increase of hormone levels of pulses recorded before treatment were compared with those recorded during treatment (the end of the third mth). No significant difference was found in serum FSH levels, yet a difference was found in serum LH levels. The pulses during the treatment nights were lower than those in the pre-treatment nights (P < 0.01). The levelling of the pulses of serum LH levels under oestriol treatment is probably an expression of the influence of oestriol on the hypothalamus-anterior-pituitary system.     

A prospective long-term study in women from pre-menopause to post-menopause: changing profiles of gonadotrophins, oestrogens and androgens

To permit a more detailed hormonal characterization of the peri-menopause, 30 healthy women were examined at regular intervals over a 7-yr period, starting about 3 yr before the menopause. Even though most of the subjects periodically experienced climacteric symptoms, no hormonal supplementation was given.

The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and oestrone that were recorded essentially confirmed previous data obtained in cross-sectional studies. Within the 6-mth period around the menopause the serum levels of testosterone and androstenedione showed small but significant decreases of 18 and 16%, respectively. These decreases continued over the following years and amounted to about 30% after 3 yr.

In contrast, neither the mean level of dehydroepiandrosterone (DHA) nor the DHA/DHA sulphate (DHAS) ratio changed significantly at the menopause, but DHA and DHAS concentrations declined slowly by about 20% over the 7-yr observation period. The mean level of DHAS showed an isolated increase during the last few months before the menopause. A similar, although not significant, increase was also seen in DHA and testosterone levels.

After the first post-menopausal year a significant positive correlation was found between the levels of oestrone and androstenedione.

This longitudinal study of individual women appeared to lend itself well to the investigation of even subtle hormonal fluctuations during the gradual transition to an established post-menopausal pattern.     

Aging does not affect the sleep endocrine response to total sleep deprivation in humans

Aging is associated with decreased sleep continuity, slow wave sleep (SWS), growth hormone (GH) release and an increased hypothalamo-pituitary-adrenocortical (HPA) system activity. Total sleep deprivation (TSD) is a strong stimulus for sleep. To determine if aging affects the response to TSD, for the first time the combined effects of TSD on conventional and spectral sleep electroencephalographic (EEG) parameters and GH, cortisol and prolactin secretion were compared in elderly (60–80 years; n = 7) vs. younger subjects (20–30 years; n = 7). MANOVA revealed a reduction of SWS in the elderly. TSD led to an increase in SWS, a decrease in sleep onset latency, rapid eye movement (REM) density and by trend REM-latency without a global group difference. GH was reduced, whereas prolactin was enhanced in the elderly. After TSD GH was unchanged and prolactin secretion was enhanced without group difference. Thus, the plasticity of the sleep-endocrine system in response to TSD is sustained during aging. The possible involvement of the GABAergic system, that seems not to be severely impaired with age, is proposed.     

Positive Feedback by Ovarian Hormones on Prolactin and LH in Old Versus Young Female Rats

The purpose of this investigation was to determine whether any differences could be demonstrated in the ability of old versus young ovariectomized rats to release prolactin and LH in response to ovarian steroid administration. Female Long Evans rats 20–24 months of age and 4 months of age were ovariectomized. Fourteen days later, each rat was injected with estradiol benzoate, followed three days later by an injection of progesterone. Blood was collected from an intra-atrial cannula for eight hrs after progesterone treatment for radioimmunoassay of prolactin and LH. Basal plasma levels of prolactin were higher in the old than in the young rats. The young rats showed a marked rise in plasma prolactin and LH in response to progesterone, whereas the old rats exhibited no elevation in prolactin and a smaller increase in LH than in young rats. Changes in hypothalamic function in the old female rats are believed to account for the differences observed.     

Positive Feedback by Ovarian Hormones on Prolactin and LH in Old Versus Young Female Rats

The purpose of this investigation was to determine whether any differences could be demonstrated in the ability of old versus young ovariectomized rats to release prolactin and LH in response to ovarian steroid administration. Female Long Evans rats 20–24 months of age and 4 months of age were ovariectomized. Fourteen days later, each rat was injected with estradiol benzoate, followed three days later by an injection of progesterone. Blood was collected from an intra-atrial cannula for eight hrs after progesterone treatment for radioimmunoassay of prolactin and LH. Basal plasma levels of prolactin were higher in the old than in the young rats. The young rats showed a marked rise in plasma prolactin and LH in response to progesterone, whereas the old rats exhibited no elevation in prolactin and a smaller increase in LH than in young rats. Changes in hypothalamic function in the old female rats are believed to account for the differences observed.     

Working hours, sleep, salivary cortisol, fatigue and neuro-behavior during Mars analog mission: five crews study

The buoyancy of humans in exploring extreme space environments has been established during missions to the moon. Long duration missions like mission to Mars however, requires humans to adapt to systemic and complex environments beyond the human body's capacity. Astronauts will encounter both physiological and psychological extremes during this trip. Very few studies are conducted on effect of long duration work and sleepiness on cognitive performance. So, this study was planned to find out effects of leadership responsibility, sleepiness and long duration working hours on cognitive performance. The 30 members (leadership: normal; 10:20) were selected from MDRS crews (Mars Desert Research Station, USA). Neurobehavioral test performance, self-ratings of fatigue and sleepiness, and salivary cortisol levels were evaluated during first day, mid and end day of mission. The leadership group did not show any signs of reduced test performance, even in elevated fatigue and sleepiness. The leadership group had faster reaction times on end of mission as compared to first and after 7 day of mission. Salivary cortisol levels were significantly higher in leadership group as compared to normal group. The results suggest that long duration work and sleepiness does not affect the cognitive performance of crew member. Further study is required while taking into account all factors and large sample size to prove this fact.     

Effects of electrochemical stimulation of medial preoptic area on prolactin and luteinizing hormone release in old female rats

Summary Serum prolactin and LH levels in old constant estrous rats were higher than in old pseudopregnant rats. Electrochemical stimulation of the medial preoptic area in old constant estrous rats resulted in significant increases in serum concentration of prolactin and LH, and subsequent ovulation. Old pseudopregnant rats showed only a small increase in serum prolactin, no increase in serum LH and no ovulation. The high circulating levels of estrogen in old constant estrous rats, and the relative lack of estrogen and the presence of progesterone in the old pseudopregnant rats, may account for the differences observed in response of the medial preoptic area to electrochemical stimulation.Aided in part by NIH research grants CA 10771 and AM 4784.     

Reciprocal control by the preoptic area of LH and prolactin

Summary Plasma levels of LH and prolactin were measured by radioimmunoassay after stimulation of the preoptic area (POA) and basal medial hypothalamus (BMH). Stimulation of the BMH resulted in increased plasma levels of LH and prolactin. In contrast, stimulation of the POA elicited increased plasma LH but produced a decrement in prolactin levels. It was concluded that the POA may be an important mediator of the often encountered reciprocal relationship between gonadotropin and prolactin release.     

Effects of recombinant LH treatment on folliculogenesis and responsiveness to FSH stimulation

BACKGROUND: The role of LH in sensitizing antral follicles to FSH is unclear. LH is required for normal hormone production and normal oocyte and embryo development, but follicular responses to LH may depend upon the stage of development. Potential roles at the early follicular phase were explored in a clinical setting by employing a sequential approach to stimulation by recombinant human (r-h) LH followed by r-hFSH in women who were profoundly down-regulated by depo GnRH agonist. METHODS: We employed a multi-centre, prospective, randomized approach. Women (n = 146) were treated in a long course high-dose GnRH agonist (Decapeptyl, 4.2 mg s.c.) protocol and were randomized to receive r-hLH (Luveris, 300 IU/day) for a fixed 7 days, or no r-hLH treatment. This was followed by a standard r-hFSH stimulation regime (Gonal-F, 150 IU/day). Ultrasound and hormone assessments of responses were measured at the start of r-hLH treatment, on FSH stimulation Days 0 and 8 and at the time of HCG administration. RESULTS: The LH treatment was associated with increased small antral follicles prior to FSH stimulation (P = 0.007), and an increased yield of normally fertilized (2 PN) embryos (P = 0.03). There was no influence of the r-hLH pretreatment upon hormone profiles or ultrasound assessments during the FSH phase. Anti-mullerian hormone increased in both groups during the week prior to FSH stimulation (P = 0.002). CONCLUSIONS: This sequential approach to the use of r-hLH in standard IVF showed a possible modest clinical benefit. The results support other recent work exploring up-regulated androgen drive upon follicular metabolism indicating that clinical benefit may be obtainable after further practical explorations of the concept.