Stephen F. Lunn

Angiogenesis and its control in the female reproductive system

The rapid, controlled and cyclical nature of angiogenesis in the female reproductive tract suggests that interference with this process should provide a novel approach to manipulation of reproductive function. Many factors involved in the regulation of angiogenesis have been identified, and the possibility of stimulating or inhibiting these paracrine control mechanisms is being addressed using current advances in the development of angiogenic and anti-angiogenic compounds. Studies with animal models indicate that the normal processes of folliculogenesis, ovulation and corpus luteum function in the ovary, and the control of menstruation and implantation in the endometrium could be profoundly influenced by manipulation of angiogenesis. Novel therapeutic agents targeted to the angiogenic pathway may also have a wide range of applications in pathological processes in the reproductive tract such as cancer, endometriosis, fibroid growth, and ovarian hyperstimulation syndrome.

Endocrine–Immune Interaction: Alterations in Immune Function Resulting From Neonatal Treatment with a GnRH Antagonist and Seasonality in Male Primates

PROBLEM: The effect of neonatal gonadotropin releasing hormone (GnRH) antagonist (Ant) treatment and seasonality on immune system development and function was investigated in male primates.
 METHOD OF STUDY: Neonatal male rhesus monkeys and marmosets were treated with Ant, and its effect on immune system morphology, circulating lymphocyte subsets, and cell‐ and humorally‐mediated immune responses was assessed during development. In adult rhesus monkeys, we correlated seasonal changes in immune function with circannual fluctuations in immunoactive hormones.
 RESULTS: In neonatal marmosets, Ant reduced the number of B cells and T cells in the thymic medulla and T cells in the periarterial lymphatic sheaths (PALS) of the spleen. Ant also altered the development of, but did not permanently impair, the proliferative index (PI) of blood lymphocytes to mitogens. In vitro treatment of control lymphocytes with GnRH analogues altered their response to these proliferative agents. In neonatal rhesus monkeys, Ant treatment increased the frequency of clinical problems, lowered circulating levels of lymphocytes, total T cells, CD8+ T cells and B cells, and altered the PI of lymphocytes to mitogens. As adults, the cell‐ and humorally‐mediated immune responses remained impaired. We also documented seasonal fluctuations in the prevalence of diseases, circulating immune cells and immune function in rhesus monkeys. The number of cases of campylobacteriosis and shigellosis was lowest in the winter and highest in the spring. Circulating numbers of white blood cells (WBC) and neutrophils and the PI of lymphocytes to mitogens were higher in the winter than in the summer. Natural killer cell activity also varied with season. Cortisol and leptin secretion exhibited circannual rhythms, rising in concert with decreasing photoperiod and increasing testicular activity in the fall. Conversely, prolactin levels declined with decreasing photoperiod and then rose in the spring.
 CONCLUSION: Neonatal exposure of male primates to Ant appears to alter early postnatal programming of immune function. In the rhesus monkey, immune function shows seasonal fluctuations that may be driven by circannual changes in the secretion of immunoactive hormones.

Does inhibin have an endocrine function during the menstrual cycle

Inhibin (alpha-beta heterodimer) has been considered to be the principal nonsteroidal ovarian regulator of pituitary FSH secretion. The beta-beta heterodimer, activin, produced by the ovary and other tissues, appears to act locally, with actions opposite to those of inhibin. Since immunoreactive inhibin is highest during the luteal phase of the menstrual cycle when FSH is lowest, a negative feedback role in controlling FSH release at this time has been suggested. Attempts to establish this by using immunoneutralization techniques have failed to reveal such a role. We must enhance our understanding of the gonadotropic control of inhibin/activin gene expression within the various compartments of the primate ovary, the role of their binding proteins, and the nature of the secretory products before we can resolve the question of whether inhibin has an endocrine function during the menstrual cycle and how cyclic reinitiation of follicular development is controlled.

Changes in lymphoid tissue after treatment with a gonadotropin releasing hormone antagonist in the neonatal marmoset (Callithrix jacchus).

PROBLEM: The effect of neonatal treatment with a gonadotropin releasing hormone (GnRH) antagonist on the morphology and distribution of lymphocytes in lymphoid tissue of the infant marmoset was examined.

Effect of neonatal treatment with a GnRH antagonist on development of the cell-mediated immune response in marmosets

PROBLEM: We examined the effect of neonatal treatment with a gonadotropin‐releasing hormone (GnRH) antagonist (antide) on the development of cell‐mediated immunity in male marmosets.