Reproductive state and motor activity in female ferrets.

The pattern of motor activity in female ferrets (Mustela putorius furo) housed in cages mounted upon rocker platforms was followed under conditions of short-(8 hr) and long-(16 hr) day illumination. A distinct diurnal rhythm was evident that remained unchanged after lesioning of the anterior hypothalamus. The level of activity did not differ between animals kept under short days and long days, between anoestrous and oestrous females, or during the development or waning of oestrus. Ovariectomy did not affect the pattern of activity. These findings are at variance with those of a previous study where wheel-running activity was followed and oestrous females found to be more active than anoestrous ferrets.

Acute effects of GnRF-induced gonadotrophin secretion upon ovarian steroid secretion in the ferret.

The effects of an increase in endogenous gonadotrophin secretion on the production of oestradiol, progesterone, androstenedione and testosterone by the ovaries of anaesthetized anoestrous and oestrous ferrets were followed. Gonadotrophin secretion was enhanced by the injection of gonadotrophin releasing factor (GnRF), and serial blood samples were collected over 9 h for hormone assay. Thyrotrophic hormone releasing factor (TRF) or acetic acid were injected for control purposes. The plasma content of oestradiol in oestrous females was significantly higher than during anoestrus, but secretion of this steroid was not increased by any means. The plasma concentration of progesterone in anoestrous females was significantly higher than during oestrus. It was increased by GnRF in anoestrous ferrets and less markedly in oestrous females. The plasma concentration of androstenedione was raised by GnRF to a greater extent during anoestrus than during oestrus. Testosterone was present in higher concentration in the plasma during anoestrus than during oestrus, and the level was increased by GnRF administration. These findings indicate that the ovaries of the anoestrous ferret secrete significant quantities of steroid hormones, and that they respond readily to gonadotrophic hormone.

Is there a critical weight for oestrus in the ferret?

Information concerning the weight at the onset of a period of oestrus, the timing of oestrus, the age at first oestrus and the lighting conditions was collected from the records of 1364 ferrets and reviewed for evidence indicating that the animals became sexually mature around a particular, critical, weight. None was found, but the results suggest that there is a minimum weight, around 420 g, below which oestrus does not occur.

Wheel-running during anoestrus and oestrus in the ferret.

Wheel-running activity was studied in female ferrets (Mustela putorius furo), during periods of anoestrus and oestrus, as well as after gonadectomy. During anoestrus wheel-running was restricted to the hours of illumination, but during oestrus extended into the dark period and was increased overall, with the number of wheel revolutions being doubled or trebled. In spayed females wheel-running was mostly limited to the light periods.

Half-life of FSH and LH in the ferret.

Anoestrous and oestrous ferrets were injected with luteinizing hormone-releasing hormone (LRH) or a long-acting analogue and subsequently hypophysectomized. Spayed ferrets were hypophysectomized without prior treatment with gonadotrophin releasing factor, and serial blood samples collected from all animals in order to follow the rate of decline in plasma gonadotrophin concentration. The half-life of LH in the spayed female (around 2 h) was much longer than that of the hormone released from the hypophysis of anoestrous females by LRH (25 min) or by the analogue (19 min). The half-life of FSH released by LRH or analogue in anoestrous females was approximately 65 min, while that discharged by the analogue in oestrous females was about 4 h. The fall in plasma FSH concentration in spayed females after hypophysectomy was too slow to allow calculation of a half-life.

Effect of exposure to long days on the secretion of oestradiol, oestrone, progesterone, testosterone, androstenedione, cortisol and follicle-stimulating hormone in intact and spayed ferrets.

The changes in concentration of plasma oestradiol, oestrone, progesterone, androstenedione, testosterone, cortisol and FSH were followed in intact female ferrets brought into oestrus by extension of the photoperiod from 8 to 16 h daily. An additional group of spayed females was similarly exposed to the extended photoperiod. There was no change in the blood oestrone, androstenedione and testosterone levels in the spayed females; the concentration of oestradiol, progesterone and FSH fell, while that of cortisol rose after 6 weeks. The intact females showed no change in plasma oestrone and cortisol concentrations, a rise in plasma oestradiol associated with the onset of oestrus, and falls in the blood levels of testosterone, androstenedione, progesterone and FSH. These results indicate that the changes in plasma gonadal steroid levels after extension of the photoperiod differ markedly from those in rodents or ruminants.

Study of prolactin levels in the ferret.

A radioimmunoassay for canine prolactin has been used to measure prolactin in the ferret. Serial dilutions of extracts of ferret pituitary glands and of ferret plasma yielded curves that were parallel with the canine prolactin standard curve. The sensitivity, accuracy, reproducibility and precision of the assay were within acceptable limits. Plasma prolactin levels increased after the administration of thyrotrophin releasing hormone (TRH) or chlorpromazine, but not after giving luteinizing hormone releasing hormone. Female ferrets, which were anoestrous, oestrous or spayed, and male ferrets had similar basal prolactin levels when sampled under sodium pentobarbitone anaesthesia. These basal levels were higher than in conscious males and the latter also showed a lesser response to TRH. Hypophysectomy significantly reduced basal prolactin levels in female ferrets by 2 h postoperatively and abolished the response to TRH.

Effect of stimulation or lesioning of the hypothalamus upon gonadotrophin secretion in the guinea-pig.

The effect of electrical stimulation of the anterior hypothalamus of the guinea-pig upon follicle-stimulating hormone (FSH) and luteinizing hormone (LH) secretion during two phases of the oestrous cycle was examined and compared with the response to electrolytic or radio-frequency lesions placed in the same area. The secretion of LH was briefly increased by electrical stimulation of the hypothalamus, with a greater response occurring over days 7-8 (luteal phase) of the oestrous cycle than on days 13-14 (follicular phase). An equivalent rise in LH output was produced by placement of direct current (d.c.) lesions in the hypothalamus, whereas lesions made with radio-frequency current produced a small increase only on days 13-14. The secretion of FSH was not changed by any procedure.

Lesions of the hypothalamic region of the fetus and length of gestation in the guinea-pig.

A lesion was placed in the hypothalamic region of the brain of one fetus in each of 25 guinea-pigs on days 39-41 of pregnancy. Thirteen females were killed before delivery and the fetuses collected for histological examination of the brain. The young of twelve other females were killed immediately after delivery in order to determine the nature and extent of any brain damage, and the findings in both groups were compared with those recorded from a series of 23 similarly operated control animals in which lesions were not made. Delivery was not consistently advanced by the brain lesions and the results do not confirm those of an earlier study in which lesions of the hypothalamus of the fetus caused premature delivery.

Lack of effect of treatment with oestrogen in advancing puberty in the guinea-pig.

Guinea-pigs were injected with 500 ng oestradiol benzoate or 0.1 ml arachis oil at 0, 5, 10, 20 or 25 days of age, or 2 microgram oestradiol benzoate/100 g body wt at 25 days, in order to determine whether puberty would be advanced, as in the rat. It was not. Repeated injections of 100 ng oestradiol benzoate or 0.1 ml arachis oil for 5 days beginning at 0, 10, 20 or 25 days of age, or 2 microgram oestradiol benzoate/100 g body wt beginning at 25 days, were similarly ineffective.

Effect of passive immunization against LH-RH on gonadotropin secretion in the ferret.

Administration of ovine antiserum containing antibodies against synthetic LH-RH to spayed female ferrets caused an immediate fall in plasma LH concentration and by 2 h after injection circulating levels had declined by 70--80%. A further decline of 50% was observed on Day 2, but by Day 4 a return to normal levels had begun and control values were regained on Day 6. In contrast, the fall in plasma FSH concentration was delayed, with a significant reduction being first observed on Day 2 and minimal values occurring on Day 4. Control values were regained by Day 7. The results accord with the concept that a single hypothalamic releasing factor controls the tonic secretion of both pituitary hormones. However, the slow change in FSH secretion implies that the mechanism for FSH release may be more autonomous than that for LH.

Repetitive treatment with gonadotrophin releasing factor or a long-acting analogue upon gonadotrophin secretion in the ferret.

The changes in plasma levels of LH and FSH were examined after treatment of intact and ovariectomized females ferrets with a long-acting analogue of gonadotrophin releasing factor (Gn-RF) (D-Ser(But)6-LH-releasing hormone (1-9)-nonapeptide ethylamide; Hoe 766) either as a single intravenous injection or daily for 6 days. The responses were compared with those induced by daily injections of Gn-RF or 0.9% NaCl (w/v). Treatment with Gn-RF consistently induced rises in both LH and FSH release with peak levels of both hormones being reached 20 min after injection and being of similar size from day to day in individual animals. Thereafter, the gonadotrophin levels declined rapidly to approach basal values by the end of each sampling period. Treatment with Hoe 766, however, produced very high values on day 1 of treatment, with LH being raised for 10-12 h and FSH for up to 24 h. Subsequent injections, on the other hand, produced an abbreviated LH response of similar size to that induced by Gn-RF and little, if any, FSH response. In ovariectomized ferrets, Hoe 766 induced a variable LH response and little FSH response at any time. In addition, basal FSH levels in the first three samples taken on each day from day 2 onwards tended to decline markedly in all of the Hoe 766-treated animals, an effect not seen in Gn-RF or 0.9% NaCl-treated controls.

Acute effects of hypothalamic lesions upon gonadotrophin secretion in the ferret.

The changes in FSH and LH secretion after placement of lesions in the hypothalamus were traced in ferrets serially bled at 15 min intervals. Passage of the lesioning current through platinum electrodes in anoestrous females was associated with an immediate surge in LH and FSH output. Damage to the hypothalamus of oestrous females also caused an immediate surge of LH secretion, but then a long-lasting second rise in blood LH content set in. High concentrations of LH were never sustained overnight. The response of long-term spayed females to the placement of hypothalamic lesions was similar to that of anoestrous ferrets, while that of anoestrous or oestrous ferrets was not altered by acute removal of the ovaries. Manipulation of the ovaries appeared to facilitate FSH and LH secretion. The response of males was similar to that of anoestrous females. Marked increases in FSH and LH release were also seen in females when lesions were made with steel electrodes, but had subsided on the following day.

Effect of anaesthesia on the negative feedback action of gonadal steroids on gonadotrophin secretion in the ovariectomized guinea-pig.

The effects of urethane or sodium pentobarbitone anaesthesia on the feedback effects of oestradiol or progesterone on gonadotrophin secretion in the ovariectomized guinea-pig have been investigated. In the control experiments in which no steroids or vehicles were given the concentration of LH and FSH in samples of peripheral blood collected at intervals of 15 min varied in a random episodic manner. The mean level of LH was significantly greater in sodium pentobarbitone- and urethane-anaesthetized animals when compared with conscious animals, and in the conscious animals there was a progressive fall in mean LH level during the course of serial sampling. This effect was not observed in anaesthetized animals. Oestradiol benzoate (2 microgram s.c.) inhibited LH secretion in conscious animals and in those anaesthetized with sodium pentobarbitone, but not in urethane-anaesthetized guinea-pigs. Progesterone (200 microgram s.c.) progressively depressed plasma LH levels in conscious and urethane-anaesthetized animals, but not in guinea-pigs anaesthetized with sodium pentobarbitone. The effect of anaesthesia was the converse of that observed with oestradiol treatment. Significant changes in FSH secretion were not observed under any experimental conditions. These findings point to the existence of a mechanism in spayed guinea-pigs that restrains LH secretion, the action of which is reduced by anaesthesia and modified by oestradiol and progesterone.

The behavioural actions of the hypothalamic peptides: a review.

Recent work has shown that the hypothalamic peptides commonly associated with the control of pituitary function have important behavioural actions of possible psychiatric significance. Thus, vasopressin, ACTH and like peptides may influence memory processes, and ACTH and MSH given intracranially induce a peculiar stretching and yawning syndrome accompanied by penile erection and ejaculation. Thyrotrophic hormone-releasing factor potentiates behavioural excitation, somatostatin is depressive, while luteinizing hormone-releasing hormone facilitates sexual behaviour and the newly identified endorphins are markedly opioid in character. These and other activities of the hypothalamic peptides are reviewed and assessed alongside the clinical information available.