The Gonads

Ovary and Testis.

THE writer has already discussed the action of androgens on individual organs before their complete differentiation. The purpose of this separation is to distinguish between the early, often permanent, effects, and the usually transient, reversible effects which androgens induce at a later stage in the life of the reproductive organs. The distinction between the two groups is not quite logical, for there is no sharply defined boundary between them. Nevertheless, in connection with human pathology and treatment—which are in the mind of the writer throughout this essay—the distinction is important; and any overlapping of thought or repetition of narrative which the arrangement entails will, the writer hopes, be forgiven.

For a long while after birth, and in some instances throughout life, the sexual characters have not assumed a fixed and final form, and some of the responses to androgen, even in late postnatal existence, are irreversible and permanent, or nearly so.

I. THE OVARY

(a) Gonadotrophic action. The first effect of androgen on the ovary of the immature animal, and perhaps on that of the adult, is an acceleration of follicular maturation. A comparable initial effect is exercised by androgens on the testis as shown by a favourable influence on spermatogenesis (p. 198).

Shapiro (1936) reported that ovulation could be induced in the clawed toad (Xenopus laevis) by various androgens as well as progesterone; and adrenal cortical extract also had this effect. The reaction was obtained even though the pituitary had been previously removed. Ovulation was not obtained in Shapiro's experiments with oestrogens; the doses of these mentioned in his paper are very large —10 mg. of oestrone and 8 mg. of oestradiol. Dantchakoff (19386) observed the formation of multiple follicular cysts in the ovaries of young guinea-pigs which had been subjected to testosterone. The condition, she says, resembles that produced by FRH, namely the simultaneous maturation of many follicles which, failing to rupture or to undergo luteinization, remain as cysts. Salmon (19386) gave single injections of 1 to 5 mg. of testosterone propionate or androstenediol in sesame oil to twelve female rats 17-30 days old. To six female rats of the same age he gave sesame oil only.

General considerations. Pituitary-adrenal relationship. Adrenal-gonad relationship. Adrenal virilism and feminism. Inactivation of deoxycorticosterone by the liver.

General Considerations

THE adrenal cortex has such an important share in the physiology of reproduction that it must be regarded as a sexual organ, though it has other than sexual functions to perform. As Kendall (1941) remarked, the adrenal cortex does not elaborate any single substance which can be described as the vital hormone of the gland. It produces numerous steroid compounds with different biological actions, and substitution therapy after adrenalectomy requires a combination of compounds.

Before considering those adrenal activities which bear directly on sexual life a few anatomical details may be recalled.

The adrenal cortex consists of three chief zones: the glomerular which is outermost, the fasciculate which is intermediate and the reticular which is inmost and immediately surrounds the medulla, which consists of nerve tissue. In young animals there is an additional zone lying next the medulla and described as the x zone (Elliott & Armour, 1911). This might perhaps be regarded not as a separate zone but as a reticular zone in its earlier form, when it differs greatly in appearance from that seen in the normal adult. Between the glomerular and fasciculate zones is a thin layer of smaller cells with condensed nuclei which has been described as the demarcation zone.

In the adult the adrenal cortex is replenished by mitoses of those glomerular cells which lie next the capsule (Zwemer, 1936; Grollman, 1936). As they pass inward from this region the cells become occupied by lipoid granules or droplets and eventually disintegrate, or disappear in some other manner, in the region of the reticular zone. In early life, and perhaps later, cell regeneration probably occurs also in or near the reticular zone. Changes in the adrenals accompany advancing age. The x zone soon disappears —during early infancy in man and about puberty in the mouse—though its disappearance may take place at different ages in the two sexes. With advanced age, especially in females, the zona fasciculata undergoes a characteristic change, the cells as they pass inward toward the medulla become increasingly laden with lipoid-like material, until as they approach the reticular region they may lose their cell walls and coalesce to form rounded masses of fat-like material containing pycnotic nuclei (Burrows, 1936b).

Effect on pituitary and on embryological development: on testis and ovary: on accessory generative organs of male and female. Co-operation and antagonism between progestin and other gonadal hormones. Similarities in action between progesterone, androgen, oestrogen and adrenal cortical hormones.

THE natural history of the corpora lutea or luteal glands having been discussed in a general way, the biological activities of their special secretions may now be considered. To avoid giving the impression that progesterone is the only effective luteal hormone, the term progestin will be used in a generic sense to include cognate compounds.

The Pituitary

Progestin, like the other gonadal hormones, acts either directly on individual organs, or indirectly affects them through the changes which it induces in the anterior lobe of the pituitary gland. These pituitary changes have been dealt with already (pp. 57,91) and need no further reference here except perhaps to recall the fact that progestin arrests the output of FRH and so interferes with the maturation of ovarian follicles and the initiation of ovarian cycles. For this purpose relatively large amounts are required.

Embryological Development

It will be remembered that both oestrogen and androgen have a pronounced influence over the development of the reproductive organs. Unfortunately we are not in a position to say much about the effects of progestin on the immature organs, for little experimental inquiry has been made into the subject. Burrows (1939 c) found that progesterone, like androgen and oestrogen, when injected into newborn female rats and mice, causes hypospadias, the ventral wall of the clitoris becoming deficient so that the opening of the urethra instead of being at its apex is at its base, level perhaps with the margin of the vaginal orifice. Burrows found also that, when persistently given to young male rats, progesterone checks the development of the testes and prevents their descent into the scrotum. Much has been done to determine what influence progesterone exerts on the development of the mamma (p. 430). Beyond these observations we know little about the effects which progesterone may have upon the growth of the reproductive organs in early life.