Experimental investigation. Chemical structure. Sources, functions and excretion. Bisexual activities. Co-operative and antagonistic effects between different hormones. Factors influencing biological action. Gradients of responsiveness. Reversible and irreversible effects. Actions common to gonadal and adrenal hormones. Influence of gonadal hormones on behaviour and on tissue growth.

THE gonadal hormones are chemical substances which regulate the male and female characters of the body, and control sexual impulse and behaviour. A conspicuous part of their function is to stimulate the growth and activity of the accessory genital organs. In the absence of these hormones the accessory organs of reproduction would not come into existence, or if already present, would not attain full development.

John Hunter (1728-1793) (1837b) perceived that the sexual characters depend largely on gonadal activity. He remarks that before puberty there is not much to distinguish the male from the female, and that the special features of the two sexes appear mostly at the time of puberty. He further notes that the female, after the reproductive period has ended, loses some of her feminine attributes and in appearance tends to approach towards the male, or more properly perhaps, he says, towards the hermaphrodite.

The output of gonadal hormones from the gonads and other organs is regulated by the pars anterior of the pituitary gland the activity of which is itself controlled, not only by the gonadal hormones formed in response to pituitary action, but by many additional influences. The complexity of the biological machinery is manifest, and it may be difficult to predict or to observe in detail all the results of disturbing any one part of the endocrine system which is concerned with reproduction.

In recent years our knowledge has rapidly extended, and, while admitting that pur comprehension of the subject is still primitive, there are now sufficient ascertained facts to allow a useful discussion.

Experimental Investigation of the Action of Gonadal Hormones

This was impeded in the past by a number of intrinsic difficulties. At the beginning the investigator had to draw conclusions from the effects of removing or transplanting whole organs or portions of them, or else from the results of injecting crude tissue extracts.

The Vagina

(a) Cornification of the vaginal epithelium. In 1917 Stockard & Papanicolaou found that a periodic cornification of the vagina occurred in certain animals and could be easily recognized by the microscopical examination of vaginal smears. A simple test was thus provided by which the sexual cycle could be followed easily and with precision. In 1923 Allen & Doisy obtained from the liquor folliculi of the sow's ovary a hormone which would induce cornification in the mouse's vagina. These two discoveries, followed as they were in 1929 by the preparation of oestrone in a pure crystalline form, have been the foundations of a great deal of subsequent research.

Oestrone given in an effective dose to a spayed mouse will produce a change in the vagina within 24 hours. An early result is a rapid multiplication of the epithelial cells, which not only increase numerically but undergo a metaplasia, so that the vagina instead of being lined by two thin layers of atrophic cells becomes lined by a squamous, keratinizing epithelium many cells in thickness. If no more oestrone be given a copious infiltration of the epithelium with leucocytes occurs, and the epithelium desquamates. On the other hand, if the dosage with oestrone is continued at sufficiently short intervals, leucocytic infiltration may be absent, so that the vagina becomes filled by a keratinous mass (Burrows & Kennaway, 1934). These vaginal changes are not equally pronounced in all animals. They are relatively inconspicuous in the rabbit, and in the mare it is said that vaginal cornification does not take place in spite of a plentiful production of oestrogen. Papanicolaou (1933) has shown that vaginal cornification occurs in women between the 8th and 12th day of the menstrual period. At this stage, he says, there is a complete or almost complete absence of leucocytes from the vaginal smears while the epithelial cells, though usually nucleated, are cornified. Mucus at this stage is abundant. He states that the commonest date for a typical oestral smear in women is the 11th day of the cycle.