The gonadotrophic hormones, LH and FSH, are synthesized in and secreted from gonadotroph cells in the anterior pituitary and comprise a common alpha-subunit and a hormone-specific beta-subunit. Gonadotrophic gene expression is activated during embryogenesis, independent of GnRH stimulation and increases as GnRH output increases, reaching adult levels at puberty. The transcriptional regulation of pituitary gonadotrophin subunit gene expression is regulated by two types of transcription factor: those that restrict and direct gene expression to gonadotrophs and those that modulate GnRH-regulated gene expression. Synergism between these two types of factor ensures gonadotroph-specific GnRH-regulated gene expression. It is not known whether these two types of transcription factor are mutually exclusive or whether they have overlapping functions. GnRH-regulated gonadotrophin subunit gene expression is modulated by transcription factors controlled by a complex interaction of GnRH, steroids and gonadal peptides, all of which bind to receptors that activate disparate intracellular signalling pathways. It remains to be established how these signalling pathways interact to transduce specific transcriptional activation of common alpha-subunit and LH and FSH beta-subunit gene expression.
P Brown and AS McNeilly
P. S. BROWN
The pituitary content of fsh was equivalent to approximately 50 μg nih. fsh sl/gland in female hamsters aged 26 days and fell to 12 μg/gland by 40 days. Male hamsters had similar levels at 26 days but the hormone content rose to 105 μg/gland by 40 days. This contrast between males and females is similar to that found in rats during sexual maturation. In guinea-pigs, pituitary fsh fell in both males and females from means of 45 and 40 μg/gland at 18 days to 15 and 12 μg/gland at 88 days. Testosterone treatment of female rats on the 5th day of life reduced pituitary fsh to 65% of normal at 28 days of age but caused no significant changes at 22, 25, 34 or 40 days.
P. S. Brown
Sundberg, Fawcett, Illner & McCann (1975) have shown that high concentrations of indomethacin (1 and 2·7 mM) can increase the release of LH and FSH from rat pituitary tissue in vitro. Such concentrations, however, have other actions in addition to the inhibition of prostaglandin (PG) synthetase for which the drug is commonly used experimentally (Flower, 1974). The effects of lower concentrations of indomethacin have therefore been tested.
LINDA FAWKE and P. S. BROWN
The follicle-stimulating hormone (fsh) content of the pituitary gland of immature female rats was equivalent to 240 μg nih-fsh-sl at the age of 22 days but had fallen to 19 μg at 40 days. In rats approaching sexual maturity, it was sometimes possible to show a significant fall in fsh between 12.00 and 18.00 hours on the same day. In adults with regular 4-day oestrous cycles, there was a significant rise in pituitary fsh content from the morning of pro-oestrus (26 μg) to the morning of oestrus (41 μg). No fall in fsh content was found during the afternoon of pro-oestrus. An Appendix describes experiments in which various methods of killing rats and storing pituitary material are compared.
P. S. BROWN and LINDA FAWKE
Drugs were injected on experimental Days 2 to 5 into mature male rats that were (1) intact, (2) castrated on Day 1, or (3) castrated on Day 1 and treated with testosterone. The animals were killed on Day 7 and the pituitary fsh content compared with that of controls. Methallibure prevented the rise in fsh content caused by testosterone in the third group and reduced pituitary fsh in intact rats: this may have resulted from inhibition of fsh synthesis. Methallibure increased pituitary fsh in castrated rats, probably by inhibiting its secretion. Reserpine increased fsh content in each type of animal and p-chlorophenylalanine increased it in all but intact rats: these drugs probably inhibit fsh secretion. The fsh content was reduced by α-methyltyrosine in testosterone-treated castrated rats while thymoxamine increased it in such animals and in intact rats. These findings do not clarify the rôle of catecholamines in fsh secretion. The similarity of the effects of reserpine and p-chlorophenylalanine supports the suggestion that 5-hydroxytryptamine plays an excitatory rôle in fsh secretion.
P. S. Brown and P. J. O'Shaughnessy
Summary. Male rats, aged 19 days, were injected with 1 mg cyproterone acetate, an antiandrogen, and killed 24 h later. In 9 out of 10 experiments this increased the apparent FSH-binding capacity by testicular tissue in vitro. In 4 out of 5 similar experiments, injection of 500 μg testosterone propionate caused a significant reduction in FSH binding. Observed changes were small but this does not preclude the possibility that androgens contribute to the physiological control of FSH receptor numbers.
BARBARA R. PEARCE and P. S. BROWN
Data on the pituitary content of follicle-stimulating hormone (fsh) in immature female rats have been published (Kragt & Ganong, 1968; Goldman & Mahesh, 1968; Fawke & Brown, 1970), but there seems to be little comparable information about the male. The following results have been obtained in males from our colony of Porton rats: the experiments were under conditions similar to those used in a previous investigation of the females (Fawke & Brown, 1970).
Three series of measurements were made (see Table 1). Results are strictly comparable within each series as they were obtained from animals born on the same day. In Series B and C, rats were randomized individually; in Series A, which involved unweaned rats, whole litters were killed together and only the allocation of litters was random. The animals
LINDA FAWKE, AUDREY MORRIS and P. S. BROWN
Compensatory hypertrophy of the remaining testis was not detected in mice hemicastrated at ages varying from 3 to 18 weeks, and killed 1, 2 or 3 weeks later. The response of hemicastrated mice to drugs and sex steroids was tested to see whether these animals were useful in studying the effects of antigonadotrophic substances. Seminal vesicle weight was significantly reduced by oestradiol, progesterone, methallibure and reserpine (though small doses of reserpine caused unexpected increases). Increase in testis weight was significantly reduced by oestradiol, methallibure, chlorpromazine and reserpine. Correction of seminal vesicle and increase in testis weight for initial body weight was found to be valid and useful. Hemicastrated mice were used to test drugs which inhibit the synthesis of biogenic monoamines: p-chlorophenylalanine reduced seminal vesicle weight but α-methyltyrosine was without effect.
J. MARTAN, Z. HRUBAN and P. BROWN
Recently, changes in cohesion of epididymal spermatozoa were reported in the flying squirrel (Martan & Hruban, 1970), grey and fox squirrels (Martan, Adams & Perkins, 1970), chinchilla (Martan, 1970a) and several other mammals, including primates (Martan, 1970b). Formations in which spermatozoa adhered tightly together by their tails or tails and heads were called cylindrical bodies. This article presents some additional observations and speculations on the formation and development of cylindrical bodies. The materials and methods involved have already been described in the above mentioned articles.
Stereocilia of principal cells protruding into the epididymal duct substantially reduce the size of the lumen. The proximal portion of the ductus epididymidis may therefore be regarded as having two lumina which differ considerably in diameter; a lumen limited by
D. V. Brown and P. L. Senger
Summary. Ejaculated spermatozoa were rendered immotile by incubation for 8 h at 37°C in 2·9% sodium citrate. Immotile spermatozoa (5 × 106) were surgically inseminated into the uterine lumen of does and samples were recovered from the uterus 5, 15, 30 and 60 min after insemination. Incubation in utero led to a resumption of progressive motility and induced head-to-head agglutination. Motility and head-to-head agglutination were highest (64 and 70% respectively) at 5 min, and declined (48 and 49%) by 60 min. The percentage of spermatozoa with an intact acrosome did not change during the in-utero incubation. When spermatozoa from a single ejaculate were evaluated in different females there was significant variation (P < 0·01) in the reinitiation of motility and agglutination. Most agglutinated spermatozoa (>96%) had an intact acrosomal membrane while acrosomal integrity of single spermatozoa differed greatly among females. We conclude that the agglutinated (motile with intact acrosomes) and non-agglutinated (usually immotile and with disrupted acrosomes) represent different populations within the uterine lumen.